International registry on the use of the CytoSorb® adsorber in ICU patients : Study protocol and preliminary results.

INTRODUCTION: The aim of this clinical registry is to record the use of CytoSorb® adsorber device in critically ill patients under real-life conditions. METHODS: The registry records all relevant information in the course of product use, e. g., diagnosis, comorbidities, course of the condition, treatment, concomitant medication, clinical laboratory parameters, and outcome (ClinicalTrials.gov Identifier: NCT02312024). Primary endpoint is in-hospital mortality as compared to the mortality predicted by the APACHE II and SAPS II score, respectively. RESULTS: As of January 30, 2017, 130 centers from 22 countries were participating. Data available from the start of the registry on May 18, 2015 to November 24, 2016 (122 centers; 22 countries) were analyzed, of whom 20 centers from four countries provided data for a total of 198 patients (mean age 60.3 ± 15.1 years, 135 men [68.2%]). In all, 192 (97.0%) had 1 to 5 Cytosorb® adsorber applications. Sepsis was the most common indication for CytoSorb® treatment (135 patients). Mean APACHE II score in this group was 33.1 ± 8.4 [range 15-52] with a predicted risk of death of 78%, whereas the observed mortality was 65%. There were no significant decreases in the SOFA scores after treatment (17.2 ± 4.8 [3-24]). However interleukin-6 levels were markedly reduced after treatment (median 5000 pg/ml before and 289 pg/ml after treatment, respectively). CONCLUSIONS: This third interim report demonstrates the feasibility of the registry with excellent data quality and completeness from 20 study centers. The results must be interpreted with caution, since the numbers are still small; however the disease severity is remarkably high and suggests that adsorber treatment might be used as an ultimate treatment in life-threatening situations. There were no device-associated side effects.

Ureteric Stenting in Kidney Transplant Recipients, Gdansk Centre Experience, Poland.

BACKGROUND: The role of ureteric stenting in kidney transplant recipients is still debatable. Stenting can reduce the incidence of urine leaks and ureter stenosis, but can be also associated with specific complications, particularly urinary tract infections (UTIs). MATERIAL AND METHODS: To estimate the influence of ureteric stenting on urological complications in kidney transplantation (KTx), we retrospectively analyzed all KTx performed between January 2011 and December 2016 in Gdansk Transplantation Centre, a total of 628 patients. Ureteric stenting was used in 502 patients (80%)-double-J (DJ) group. Catheters were implanted during the surgical procedure and left in situ for a mean time of 30 days. RESULT: The frequency of urinary leaks was 10 times higher in patients without stenting (10%). Ureter stenosis was also more frequent in the non-DJ group (8.7% vs 1.6%, P < .05). Multiple-regression modeling showed that the urinary not stenting was a risk factor for urinary leak (adjusted odds ratio [AOR] = 0,1; 95% confidence interval [CI]: 0.03-0.26; P < .01), ureter stenosis (AOR = 0,16; 95% CI: 0.06-0.41; P < .01), and generally reoperation after KTx (AOR = 0,46; 95% CI: 0.28-0.77; P < .01). Acute rejection and delayed graft function were equal in both groups. Mean serum creatinine concentration 1 month after transplantation was similar in both groups (1.5 mg/dL in the DJ group and 1.44 mg/dL in the non-DJ group, P > .05). UTIs were more frequent in the DJ group (22.1% vs 16.7%), but the difference was not significant. Time of hospitalization was longer in patients with UTI (34 vs 22 days, P < .05). CONCLUSIONS: Ureteric stenting can protect patients from most frequent urological complications like urine leaks and ureter stenosis. The influence of ureteric stenting on UTI development is not strong in our material.

[Expenditure on the Care of COPD Patients Under Everyday Conditions in Pneumological Practices Differentiated According to Patients in Chronic Care and New Patients and Severity of the Illness]. / Aufwand bei der Betreuung von COPD-Patienten unter Alltagsbedingungen in pneumologischen Praxen differenziert nach bekannten und neuen Patienten und nach Schweregraden der Erkrankung.

New patients in the secondary respiratory care require more time for the first consultation and place a higher diagnostic and therapeutic demand if compared to patients already in chronic care. More diagnostic procedures and patient's education by the team are required. No such burden is observed regarding differential degrees of severity of respiratory diseases, e. g. COPD. The overall demands add up to twice the demands of patients already in care. Thus the time required for the treatment of 50 new patients allows consultations for 100 patients already known in the office.As additional time and effort for new patients is not adequately represented in the German medical tax (EBM) a trend to risk selection and a preference for control patients is observed. In contrast incentives to foster treatment of new patients could be an effective measure to dramatically reduce waiting time for visits with pulmonologists. This should be achieved by changes in the German medical tax (EBM).

Treatment-free remission following frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the ENESTfreedom study.

The single-arm, phase 2 ENESTfreedom trial assessed the potential for treatment-free remission (TFR; i.e., the ability to maintain a molecular response after stopping therapy) following frontline nilotinib treatment. Patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase with MR4.5 (BCR-ABL1⩽0.0032% on the International Scale (BCR-ABL1IS)) and ⩾2 years of frontline nilotinib therapy were enrolled. Patients with sustained deep molecular response during the 1-year nilotinib consolidation phase were eligible to stop treatment and enter the TFR phase. Patients with loss of major molecular response (MMR; BCR-ABL1IS⩽0.1%) during the TFR phase reinitiated nilotinib. In total, 215 patients entered the consolidation phase, of whom 190 entered the TFR phase. The median duration of nilotinib before stopping treatment was 43.5 months. At 48 weeks after stopping nilotinib, 98 patients (51.6%; 95% confidence interval, 44.2-58.9%) remained in MMR or better (primary end point). Of the 86 patients who restarted nilotinib in the treatment reinitiation phase after loss of MMR, 98.8% and 88.4%, respectively, regained MMR and MR4.5 by the data cutoff date. Consistent with prior reports of imatinib-treated patients, musculoskeletal pain-related events were reported in 24.7% of patients in the TFR phase (consolidation phase, 16.3%).

[Positionpaper on Telemonitoring in Sleep-Related Breathing Disorders]. / Positionspapier zum Telemonitoring bei schlafbezogenen Atmungsstörungen.

The use of telemonitoring in the care of patients with Sleep-related Breathing Disorders (SBD) can enhance medical support significantly. Telemonitoring aims at helping physicians to detect therapy problems early and thus improve patients' therapy adherence. Diagnostics and therapy decisions in the telemonitoring process nevertheless remain the responsibility of sleep specialists. The selection of data monitored, their evaluation and resulting consequences fall to the physician, who makes decisions and prescribes therapy in consultation with the patient. In light of professional legal and ethical requirements, it must be ensured that the extensive changes to the process flow in sleep medicine are designed in a way to guarantee high-quality patient care. In this position paper, the German Sleep Society, the German Respiratory Society, the Association of Pneumological Hospitals and the Federal Association of German Pneumologists comment on important aspects for implementation of telemonitoring for SRBD and describe the basic conditions required for its use.

Treatment and outcome of 2904 CML patients from the EUTOS population-based registry.

The European Treatment and Outcome Study (EUTOS) population-based registry includes data of all adult patients newly diagnosed with Philadelphia chromosome-positive and/or BCR-ABL1+ chronic myeloid leukemia (CML) in 20 predefined countries and regions of Europe. Registration time ranged from 12 to 60 months between January 2008 and December 2013. Median age was 55 years and median observation time was 29 months. Eighty percent of patients were treated first line with imatinib, and 17% with a second-generation tyrosine kinase inhibitor, mostly according to European LeukemiaNet recommendations. After 12 months, complete cytogenetic remission (CCyR) and major molecular response (MMR) were achieved in 57% and 41% of patients, respectively. Patients with high EUTOS risk scores achieved CCyR and MMR significantly later than patients with low EUTOS risk. Probabilities of overall survival (OS) and progression-free survival for all patients at 12, 24 and 30 months was 97%, 94% and 92%, and 95%, 92% and 90%, respectively. The new EUTOS long-term survival score was validated: the OS of patients differed significantly between the three risk groups. The probability of dying in remission was 1% after 24 months. The current management of patients with tyrosine kinase inhibitors resulted in responses and outcomes in the range reported from clinical trials. These data from a large population-based, patient sample provide a solid benchmark for the evaluation of new treatment policies.

Treatment of the Lymphocele After Kidney Transplantation: A Single-center Experience.

BACKGROUND: Lymphocele is one of the most common complications after kidney transplantation. It is usually asymptomatic, but can cause pressure on the kidney transplant, ureter, bladder, and adjacent vessels with deterioration of graft function, ipsilateral leg edema, and external iliac vein thrombosis. Peritoneal fenestration is a well-established method for treatment. In this report, we present the incidence of symptomatic lymphocele requiring treatment (LRT), demographic and surgical factors that influenced lymphocele formation, its clinical presentation, and 2 types of treatment: open and laparoscopic intraperitoneal drainage in the experience of our center. MATERIAL AND METHODS: We retrospectively analyzed all kidney transplantations performed between January 2007 and December 2014 in Gdansk Transplantation Center (n = 740) and selected patients with LRT. LRT occurred in 59 cases (8%). All other patients transplanted during the same time (n = 681) were treated as a control group in the univariate and multivariate analysis of risk factors of the lymphocele formation. RESULTS: Surgical intraperitoneal drainage was performed in an open method in 53 cases and laparoscopically in 6 patients. We observed recurrence of lymphocele in 11 cases (18.6%). Acute rejection episodes (ARE) and delayed graft function (DGF) were more frequent in patients with LRT. ARE and age were independent risk factors for LRT in multivariate analysis. The mean estimated glomerular filtration rate by the Modification of Diet in Renal Disease method at 1 month after the fenestration was higher than before the operation (51.7 and 43.6 mL/min, respectively). CONCLUSIONS: Fenestration is a safe and effective method of treatment of symptomatic lymphocele. ARE, DGF, and older age were associated with a greater risk of LRT.

The effect of peer review on mortality rates.

OBJECTIVE: Lowering of mortality rates in hospitals with mortality rates higher than accepted reference values for acute myocardial infarction (AMI), congestive heart failure (CHF), pneumonia, stroke, mechanical ventilation (MV) and colorectal surgery by using an external peer review process that identifies areas requiring rectification and implements protocols directed at improving these areas. DESIGN: Retrospective, observational, quality management study using administrative data to compare in-hospital mortality rates (pre and post an external peer review process that included adoption of improvement protocols) with reference values. SETTING: German general hospitals of a large, private group. PARTICIPANTS: Hospitals with mortality rates higher than reference values. INTERVENTIONS: Peer review of medical records by experienced, outside physicians triggered by in-hospital mortality rates higher than expected. Inadequacies were identified, improvement protocols enforced and mortality rates subsequently re-examined. MAIN OUTCOME MEASURES: Mortality rates 1 year before and 1 year after peer review and protocol use. RESULTS: For AMI, CHF, pneumonia, stroke, MV and colorectal surgery, the mortality rates 1 year post-peer review were significantly decreased as compared to pre-peer review mortality rates. The standardized mortality ratio for all of the above diagnoses was 1.45, 1 year before peer review, and 0.97, 1 year after peer review. The absolute risk reduction of 7.3% translates into 710 deaths in this population which could have been prevented. CONCLUSIONS: Peer review triggered and conducted in the manner described here is associated with a significant lowering of in-hospital mortality rates in hospitals that previously had higher than expected mortality rates.

[Cannabis--Position Paper of the German Respiratory Society (DGP)]. / Cannabis--Positionspapier der Deutschen Gesellschaft für Pneumologie und Beatmungsmedizin e.V. (DGP).

In this position paper, the adverse health effects of cannabis are reviewed based on the existing scientific literature; in addition possible symptom-relieving effects on some diseases are depicted. In Germany, cannabis is the most widely used illicit drug. Approximately 600,000 adult persons show abusive or addictive cannabis consumption. In 12 to 17 year old adolescents, cannabis use increased from 2011 to 2014 from 2.8 to 6.4%, and the frequency of regular use from 0.2 to 1.5%. Currently, handling of cannabinoids is much debated in politics as well as in general public. Health aspects have to be incorporated into this debate. Besides analysing mental and neurological side effects, this position paper will mainly focus on the influences on the bronchopulmonary and cardiovascular system. There is strong evidence for the induction of chronic bronchitis. Allergic reactions including asthma are known, too. Associations with other diseases like pulmonary emphysema, lung cancer and pneumonia are not sufficiently proven, however cannot be excluded either. In connection with the use of cannabis cardiovascular events such as coronary syndromes, peripheral vascular diseases and cerebral complications have been noted. Often, the evidence is insufficient due to various reasons; most notably, the overlapping effects of tobacco and cannabis use can frequently not be separated adequately. Empirically, early beginning, high-dosed, long-lasting and regular cannabis consumption increase the risk of various psychological and physical impairments and negatively affect age-based development. Concerns therefore relate especially to children and adolescents. There is only little scientific evidence for medical benefits through cannabis as a remedy; systematic research of good quality, in particular prospective, randomised, placebo-controlled double-blinded studies are rare. The medical societies signing this position paper conclude that cannabis consumption is linked to adverse health effects which have to be taken into consideration in the debate about the social attitude towards cannabinoids. The societies agree that many aspects regarding health effects of cannabis are still uncertain and need clarification, preferably through research provided by controlled studies.

Quality of Life After Kidney Transplantation: A Prospective Study.

BACKGROUND: The purpose of renal transplantation is to achieve a maximal improvement in quality of life (QoL) and life expectancy in patients with end-stage renal disease (ESRD) while minimizing the potential side effects of this procedure. It is important to achieve an optimal balance between graft function and the patient's QoL. This study was designed to assess the changes in the QoL after kidney transplantation (KTx) in patients with ESRD previously treated with hemodialysis (HD) or peritoneal dialysis (PD). METHODS: QoL was prospectively analyzed in 69 patients after kidney transplantation in a single-center study. Patients with ESRD were divided into 2 groups: those previously treated with HD (n = 44 patients; group 1) or PD (n = 25 patients; group 2). Both groups were asked to complete the KDQOL-SFtm questionnaire before and 12 months after kidney transplantation. RESULTS: We observed significant differences in many parameters of QoL in both groups after KTx but more positive changes of most parameters in question exhibited by patients previously treated by means of HD than PD. Patients treated with HD and PD demonstrated improvement after KTx in 74% of dimensions. There were no statistical differences in the QoL between group 1 and group 2 before or after KTx. CONCLUSIONS: The study demonstrated post- to pre-transplant improvements of QoL independently of previous treatment.

Frontline nilotinib in patients with chronic myeloid leukemia in chronic phase: results from the European ENEST1st study.

The Evaluating Nilotinib Efficacy and Safety in Clinical Trials as First-Line Treatment (ENEST1st) study included 1089 patients with newly diagnosed chronic myeloid leukemia in chronic phase. The rate of deep molecular response (MR(4) (BCR-ABL1⩽0.01% on the International Scale or undetectable BCR-ABL1 with ⩾10,000 ABL1 transcripts)) at 18 months was evaluated as the primary end point, with molecular responses monitored by the European Treatment and Outcome Study network of standardized laboratories. This analysis was conducted after all patients had completed 24 months of study treatment (80.9% of patients) or discontinued early. In patients with typical BCR-ABL1 transcripts and ⩽3 months of prior imatinib therapy, 38.4% (404/1052) achieved MR(4) at 18 months. Six patients (0.6%) developed accelerated or blastic phase, and 13 (1.2%) died. The safety profile of nilotinib was consistent with that of previous studies, although the frequencies of some nilotinib-associated adverse events were lower (for example, rash, 21.4%). Ischemic cardiovascular events occurred in 6.0% of patients. Routine monitoring of lipid and glucose levels was not mandated in the protocol. These results support the use of frontline nilotinib, particularly when achievement of a deep molecular response (a prerequisite for attempting treatment-free remission in clinical trials) is a treatment goal.

Long-term outcome of patients with newly diagnosed chronic myeloid leukemia: a randomized comparison of stem cell transplantation with drug treatment.

Tyrosine kinase inhibitors represent today's treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69-0.82) vs 0.69 (95% CI: 0.61-0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.

The EUTOS population-based registry: incidence and clinical characteristics of 2904 CML patients in 20 European Countries.

This population-based registry was designed to provide robust and updated information on the characteristics and the epidemiology of chronic myeloid leukemia (CML). All cases of newly diagnosed Philadelphia positive, BCR-ABL1+ CML that occurred in a sample of 92.5 million adults living in 20 European countries, were registered over a median period of 39 months. 94.3% of the 2904 CML patients were diagnosed in chronic phase (CP). Median age was 56 years. 55.5% of patients had comorbidities, mainly cardiovascular (41.9%). High-risk patients were 24.7% by Sokal, 10.8% by EURO, and 11.8% by EUTOS risk scores. The raw incidence increased with age from 0.39/100,000/year in people 20-29 years old to 1.52 in those >70 years old, and showed a maximum of 1.39 in Italy and a minimum of 0.69 in Poland (all countries together: 0.99). The proportion of Sokal and Euro score high-risk patients seen in many countries indicates that trial patients were not a positive selection. Thus from a clinical point of view the results of most trials can be generalized to most countries. The incidences observed among European countries did not differ substantially. The estimated number of new CML cases per year in Europe is about 6370.

The use of Tenckhoff catheters for draining of symptomatic lymphoceles: a review of literature and our experience.

BACKGROUND: Lymphoceles are one of the common complications of kidney transplantations. While small, asymptomatic lypmhoceles do not require intervention, however, larger, high-pressure cases can lead to graft dysfunction and are thus an indication for decompression. The aim of this study is to present the drainage using a Tenckhoff catheter as effective treatment for recurrence of symptomatic lymphoceles based on both a single center's experience as well as existing literature. MATERIALS AND METHODS: In our database, two patients were operated with a Tenckhoff catheter for the recurrence of symptomatic lymphocele. A review of MEDLINE in search of cases with lymphoceles treated with Tenckhoff catheterization yielded only five articles published between 1990 and 2014. The reports covered 15 cases in which 11 patients were treated for a primary lymphocele whereas 4 were treated for a recurring lymphocele. RESULTS: There was no evidence of lymphocele recurrence or infections after Tenckhoff catheterization in either the material review or our database. CONCLUSIONS: Intraperitoneal drainage with a Tenckhoff catheter seems to be an effective and safe method for treating recurrent, symptomatic lymphoceles after renal transplantation.

[Daily care of patients with asthma in the pulmonary practice: changes in asthma - control and therapy depending on the initial level of control]. / Alltagsversorgung von Patienten mit Asthma in der pneumologischen Praxis: Veränderungen des Asthma-Kontrollgrades und der Therapie in Abhängigkeit vom ursprünglichen Kontrollgrad.

To assess the quality of treatment of patients with asthma who were treated jointly by pulmonologists and the family doctor, a data analysis was performed in 13 asthma specialists in 894 asthmatics and a written survey of patients after 3 months of treatment.The data analysis related to the current therapy, the therapy changes and the changes in asthma control test (ACT). One focus of the investigation was placed on the separate analysis of patients with controlled and uncontrolled asthma. Both patient groups show both decrease, as well as increases in the number of points of the ACT. In patients with non-controlled asthma, the proportion of an increase in the number of points in the ACT is above average and indicates an improvement of the disease. This is operated in the patient's subjective assessment. In both patient groups there is a large proportion of patients who report a subjective improvement. An improvement is usually achieved by an improved pharmacotherapy, a deterioration usually occurs due to external influences. The differences for the patient groups are here but less significantly. There is a general satisfaction with both the drug therapy, as well as with the handling. The inhalation drug therapy is performed very stable. In patients with poor asthma control therapy is usually intensified. In oral pharmacotherapy oral steroid therapy has a great dynamic in patients with uncontrolled asthma. In this group, the most frequent increases in the dose of inhaled substances are recorded.

Forensic animal DNA typing: Allele nomenclature and standardization of 14 feline STR markers.

Since the domestic cat (Felis catus) has become one of the most popular pets and owners usually develop a close relationship to their cats, it is necessary to take traces of cats into account for forensic casework. For this purpose feline short tandem (STR) repeat markers have been investigated in several earlier studies, but no detailed description of sequence data, allelic variations or a repeat-based nomenclature is available. The aim of the study was to provide a suggestion for the allele nomenclature of 14 cat STR markers according to the recommendations of the International Society for Forensic Genetics (ISFG) for human DNA typing and to present a standardized system for a secure DNA typing of samples. Samples of 122 unrelated cats from a local animal shelter and private owners in Germany were used to generate a population database with allele frequencies and to analyze the tandemly repeated sequence variations within the alleles of each STR marker. These markers could be grouped into two STR classes: simple repeat STRs and complex STRs (some with the supplement highly complex), consisting of di- and tetranucleotide repeat motifs. After analyzing the repeat structure and elaborating a repeat based nomenclature, allelic ladders of common and rarely occurring alleles for each marker were designed to enable accurate typing of alleles that differ in fragment length and to facilitate data exchange.

[Therapy adherence in bronchial asthma patients: Healthcare under everyday conditions in pulmonological practices]. / Therapieadhärenz bei Asthma bronchiale - Versorgung unter Alltagsbedingungen in der pneumologischen Praxis.

In the present study, patients with asthma were interviewed with regard to their treatment adherence. It was shown that adherence is significantly influenced by age, occupation, quality of information about the disease and interest of the patient in disease, mode of action and use of the inhalation device. Younger, working patients who do not feel "completely adequately" informed are more likely to be not-adherent. Each aspect should be noted separately.The characterization enables forming target groups for appropriate counselling initiatives in pulmonology practice and allows the effectiveness of the measures to be examined. The results confirm the importance of doctor/patient communication for achieving a high level of adherence and thus therapeutic success.It is suggested that, in addition to questionnaires already in use, asthma patients should be given the following questions in writing during routine monitoring of therapy; based on the results of the survey, the extent of advice necessary can be determined -Do you feel sufficiently informed about your illness? -Do you feel sufficiently informed about the effect of the drug therapy? -Do you feel sufficiently informed about the handling of the inhalation drugs? -Are you satisfied with the handling of your inhalation medication? The following options to answer the questions should be available: completely - mainly - somewhat - not at all. There were significant differences in adherence between patients who were completely satisfied with the handling of their device and those that were not. However, there was no significant difference between the devices. Therefore, the same therapy adherence can be predicted for all devices when the device is suitable for the patient and also provides complete satisfaction in handling. Since it is the subjective perception of patients, the data show significant differences between study centres. These were mirrored in a blind benchmark to stimulate improvements.

Validation of two canine STR multiplex-assays following the ISFG recommendations for non-human DNA analysis.

To gain general acceptance forensic DNA testing in animals needs to improve standardization of analysis methods and data interpretation. Recently, the International Society of Forensic Genetics (ISFG) took particular care of this topic by publishing recommendations for forensic non-human DNA analysis following the successful example of human DNA analysis in order to provide a basis for harmonization of the still existing inter-laboratory variability. By following these recommendations we demonstrate the performance of two short tandem repeat (STR) multiplexes for forensic identity testing of canine biological material. Thirteen STRs and two sex-specific markers were selected and validated according to the ISFG guidelines. Population genetic parameters were calculated based on 295 dog samples collected in Austria (124) and Germany (171). A repeat-based nomenclature of the mainly tetrameric STRs and corresponding allelic ladders are presented. All 146 different alleles included in the ladders were sequenced for correct allele calling. Additionally, a canine cell line (DH82-D3167) was evaluated as standard reference material.