[The use of botulinum toxin in hernia surgery: results of a survey in certified hernia centers]. / Die Anwendung von Botulinumtoxin in der Hernienchirurgie: Ergebnisse einer Umfrage an zertifizierten Hernienzentren.

BACKGROUND: Botulinum toxin application into the abdominal wall prior to major hernia repair can reduce the complexity of surgery and has been increasingly used in recent years, even if it is an off-label use. OBJECTIVE: To what extent is botulinum toxin used in hernia surgery in German-speaking countries and what is the current evidence in the literature? MATERIAL AND METHODS: In a voluntary online survey of German Society for General and Visceral Surgery (DGAV)-certified competence centers and reference centers for hernia surgery, aspects of botulinum toxin application were surveyed and the results analyzed. RESULTS: A total of 57 centers took part in the survey, of which 27 (47%) use botulinum toxin. The main reasons for not using it were lack of experience and reimbursement. Of the centers 85% have treated less than 50 patients with botulinum toxin. The main indications were midline hernias (M2-4 according to the EHS classification) with a hernia gap > 10 cm (W3 according to EHS classification) and loss of domain situations. The application was predominantly ultrasound-guided by designated hernia surgeons with 100-200 Allergan or 500 Speywood units 4-6 weeks preoperatively and without complications related to the botulinum toxin application. CONCLUSION: Botulinum toxin injections in hernia surgery appear to be safe and effective. Ultrasound-guided preoperative bilateral administration is supported by the available data. Specific course and information formats should be offered by the hernia surgery institutions.

Analysis of surgical quality indicators after certification as a Hernia Center.

Certifications are an increasingly used tool of quality management in the health care system. The primary goal is to improve the quality of treatment due to implemented measures based on a defined catalog of criteria and standardization of the treatment processes. However, the extent to which this affects medical and health-economic indicators is unknown. Therefore, the study aims to examine the possible effects of the certification as a Reference Center for Hernia Surgery on the treatment quality and reimbursement dimensions. The observation and recording periods were defined as 3 years before (2013-2015) and 3 years after certification as a "Reference Center for Hernia Surgery" (2016-2018). Possible changes due to the certification were examined based on multidimensional data collection and analysis. In addition, the aspects of structure, process and result quality, and the reimbursement situation were reported. One thousand three hundred and nineteen cases before and one thousand four hundred and three cases after certification were included. After the certification, the patients were older (58.1 ± 16.1 vs. 64.0 ± 16.1 years, p < 0.01), had a higher CMI (1.01 vs. 1.06), and a higher ASA score (< III 86.9 vs. 85.5%, p < 0.01). The interventions became more complex (e.g., recurrent incisional hernias 0.5% vs. 1.9%, p < 0.01). The mean length of hospital stay was significantly reduced for incisional hernias (8.8 ± 5.8 vs. 6.7 ± 4.1 days, p < 0.001). The reoperation rate for incisional hernias also decreased significantly from 8.24 to 3.66% (p = 0.04). The postoperative complication rate for inguinal hernias was significantly reduced (3.1 vs. 1.1%, p = 0.002). The reimbursement of the hernia center increased by 27.6%. There were positive changes in process and outcome quality and reimbursement after the certification, which supports the effectivity of certifications in hernia surgery.

Liquid Biopsy in Organ Damage: small extracellular vesicle chip-based assessment of polytrauma.

Background: Despite major advances in medicine, blood-borne biomarkers are urgently needed to support decision-making, including polytrauma. Here, we assessed serum-derived extracellular vesicles (EVs) as potential markers of decision-making in polytrauma. Objective: Our Liquid Biopsy in Organ Damage (LiBOD) study aimed to differentiate polytrauma with organ injury from polytrauma without organ injury. We analysed of blood-borne small EVs at the individual level using a combination of immunocapture and high-resolution imaging. Methods: To this end, we isolated, purified, and characterized small EVs according to the latest Minimal Information for Studies of Extracellular Vesicles (MISEV) guidelines from human blood collected within 24 h post-trauma and validated our results using a porcine polytrauma model. Results: We found that small EVs derived from monocytes CD14+ and CD14+CD61+ were significantly elevated in polytrauma with organ damage. To be precise, our findings revealed that CD9+CD14+ and CD14+CD61+ small EVs exhibited superior performance compared to CD9+CD61+ small EVs in accurately indicating polytrauma with organ damage, reaching a sensitivity and a specificity of 0.81% and 0.97%, respectively. The results in humans were confirmed in an independent porcine model of polytrauma. Conclusion: These findings suggest that these specific types of small EVs may serve as valuable, non-invasive, and objective biomarkers for assessing and monitoring the severity of polytrauma and associated organ damage.

SCAview: an Intuitive Visual Approach to the Integrative Analysis of Clinical Data in Spinocerebellar Ataxias.

With SCAview, we present a prompt and comprehensive tool that enables scientists to browse large datasets of the most common spinocerebellar ataxias intuitively and without technical effort. Basic concept is a visualization of data, with a graphical handling and filtering to select and define subgroups and their comparison. Several plot types to visualize all data points resulting from the selected attributes are provided. The underlying synthetic cohort is based on clinical data from five different European and US longitudinal multicenter cohorts in spinocerebellar ataxia type 1, 2, 3, and 6 (SCA1, 2, 3, and 6) comprising > 1400 patients with overall > 5500 visits. First, we developed a common data model to integrate the clinical, demographic, and characterizing data of each source cohort. Second, the available datasets from each cohort were mapped onto the data model. Third, we created a synthetic cohort based on the cleaned dataset. With SCAview, we demonstrate the feasibility of mapping cohort data from different sources onto a common data model. The resulting browser-based visualization tool with a thoroughly graphical handling of the data offers researchers the unique possibility to visualize relationships and distributions of clinical data, to define subgroups and to further investigate them without any technical effort. Access to SCAview can be requested via the Ataxia Global Initiative and is free of charge.

[Physical Strain after Abdominal Surgery - Results of a Patient Survey]. / Belastbarkeit nach abdominellen Eingriffen ­ Ergebnisse einer Patientenbefragung.

INTRODUCTION: Incision hernias are common complications after abdominal surgery and affect the recommendations on postoperative physical strain, as it is thought that excessively early strain causes incisional hernias. However, there is no evidence to justify this. This study evaluates the effect of postoperative strain on the risk of incisional hernia. MATERIALS AND METHODS: Patients with a laparoscopy (LS) or laparotomy (LT) were asked to complete a questionnaire on postoperative strain, complaints and quality of life. Patients with hernia surgery, or open abdomen therapy for complicated courses (Clavien-Dindo > III) were excluded. RESULTS: 393 patients completed the questionnaire (43.6%). 274 were LS and 128 LT. The incidence of incisional hernias was 5.2% (LS) and 18.0% (LT, p = 0.001). Incisional hernia patients were younger and more commonly males. 30.5% of incisional hernia patients did not return to normal physical strain postoperatively. Abdominal binders did not affect the hernia rate. The incisional hernia patients showed decreased quality of life scores in both mental and physical domains. CONCLUSION: Early postoperative physical strain was not a risk factor for incisional hernia development in this study. However, prospective studies are needed to create necessary evidence to recommend earlier postoperative return to normal physical strain.

Traumatic diaphragmatic rupture: epidemiology, associated injuries, and outcome-an analysis based on the TraumaRegister DGU®.

INTRODUCTION: Traumatic diaphragmatic rupture is a rare injury in the severely injured patient and is most commonly caused by blunt mechanisms. However, penetrating mechanisms can also dominate depending on regional and local factors. Traumatic diaphragmatic rupture is difficult to diagnose and can be missed by primary diagnostic procedures in the resuscitation room. Initially not life-threatening, diaphragmatic ruptures can cause severe sequelae in the patient's long-term course if untreated. The objective of this study was to assess the epidemiology, associated injuries, and outcome of traumatic diaphragmatic ruptures based on a multicenter registry-based analysis. MATERIAL AND METHODS: Data from all patients enrolled in the TraumaRegister DGU® between 2009 and 2018 were retrospectively analyzed. That multicenter database collects data on prehospital, intra-hospital emergency, intensive care therapy, and discharge. Included were all patients with a Maximum Abbreviated Injury Scale (MAIS) score of 3 or above and patients with a MAIS score of 2 who died or were treated in the intensive care unit, for whom standard documentation forms had been completed and who had sustained a diaphragmatic rupture (AIS score of 3 or 4). The data has been analyzed using descriptive statistics and chi-square test or Mann-Whitney U test. RESULTS: Of the 199,933 patients included in the study population, 687 patients (0.3%) had a diaphragmatic rupture. Of these, 71.9% were male. The mean patient age was 46.1 years. Blunt trauma accounted for 73.5% of the injuries. Primary diagnosis was established in the resuscitation room in 93.1% of the patients. Multislice helical computed tomography (MSCT) was performed in 82.7% of the cases. Rib fractures were detected in 60.7% of the patients with a diaphragmatic injury. Patients with diaphragmatic rupture had a higher mean Injury Severity Score (ISS) than patients without a diaphragmatic injury (32.9 vs. 18.6) and a higher mortality rate (13.2% vs. 9.0%). CONCLUSIONS: In contrast to the literature, primary diagnostic procedures in the resuscitation room detected relevant diaphragmatic ruptures (AIS ≥ 3) in more than 90% of the patients in our study population. In addition, complex associated serial rib fractures are an important diagnostic indicator.

Integrative data semantics through a model-enabled data stewardship.

MOTIVATION: The importance of clinical data in understanding the pathophysiology of complex disorders has prompted the launch of multiple initiatives designed to generate patient-level data from various modalities. While these studies can reveal important findings relevant to the disease, each study captures different yet complementary aspects and modalities which, when combined, generate a more comprehensive picture of disease etiology. However, achieving this requires a global integration of data across studies, which proves to be challenging given the lack of interoperability of cohort datasets. RESULTS: Here, we present the Data Steward Tool (DST), an application that allows for semi-automatic semantic integration of clinical data into ontologies and global data models and data standards. We demonstrate the applicability of the tool in the field of dementia research by establishing a Clinical Data Model (CDM) in this domain. The CDM currently consists of 277 common variables covering demographics (e.g. age and gender), diagnostics, neuropsychological tests and biomarker measurements. The DST combined with this disease-specific data model shows how interoperability between multiple, heterogeneous dementia datasets can be achieved. AVAILABILITY AND IMPLEMENTATION: The DST source code and Docker images are respectively available at https://github.com/SCAI-BIO/data-steward and https://hub.docker.com/r/phwegner/data-steward. Furthermore, the DST is hosted at https://data-steward.bio.scai.fraunhofer.de/data-steward. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Deep Learning-based detection of psychiatric attributes from German mental health records.

BACKGROUND: Health care records provide large amounts of data with real-world and longitudinal aspects, which is advantageous for predictive analyses and improvements in personalized medicine. Text-based records are a main source of information in mental health. Therefore, application of text mining to the electronic health records - especially mental state examination - is a key approach for detection of psychiatric disease phenotypes that relate to treatment outcomes. METHODS: We focused on the mental state examination (MSE) in the patients' discharge summaries as the key part of the psychiatric records. We prepared a sample of 150 text documents that we manually annotated for psychiatric attributes and symptoms. These documents were further divided into training and test sets. We designed and implemented a system to detect the psychiatric attributes automatically and linked the pathologically assessed attributes to AMDP terminology. This workflow uses a pre-trained neural network model, which is fine-tuned on the training set, and validated on the independent test set. Furthermore, a traditional NLP and rule-based component linked the recognized mentions to AMDP terminology. In a further step, we applied the system on a larger clinical dataset of 510 patients to extract their symptoms. RESULTS: The system identified the psychiatric attributes as well as their assessment (normal and pathological) and linked these entities to the AMDP terminology with an F1-score of 86% and 91% on an independent test set, respectively. CONCLUSION: The development of the current text mining system and the results highlight the feasibility of text mining methods applied to MSE in electronic mental health care reports. Our findings pave the way for the secondary use of routine data in the field of mental health, facilitating further clinical data analyses.

[Diagnosis and Treatment of Severe Fournier's Gangrene: Introduction of a Surgical Approach, Evaluation of Risk Factors, Microbiological Characteristics and Review of the Literature]. / Diagnose und zielgerichtete Therapie der Fournier-Gangrän mit septischem Verlauf: Vorstellung eines Behandlungsalgorithmus, Identifikation von Risikofaktoren, Betrachtung des Mikrobioms und Abgleich mit der Literatur.

BACKGROUND: Fournier's gangrene is a necrotising fasciitis type I occurring in the perineal and genital region. The disease expands progressively and still has poor outcome, especially in critical ill patients. This study's focus was placed on the evaluation of risk factors and comorbidities, on the bacteriological spectrum, laboratory analyses, mortality and the course according to the algorithmic approach. METHOD: The medical records were reviewed of 10 patients with severe Fournier's gangrene from 2010 to 2019 who underwent intensive care therapy for at least 48 hours. Ten patients with Fournier's gangrene and sepsis and intensive therapy lasting at least 48 hours were recorded and analysed descriptively. RESULTS: The patient cohort consisted of six men and four women with a median age of 62 years (range 42 - 78 years). The median time between the onset of symptoms and hospitalisation was four days (range 3 - 5 days). The commonest aetiological event was a minor trauma. Predisposing factors included diabetes mellitus (30%) and overweight (80% BMI > 25). 90% of patients exhibited polymicrobial infection. All patients had systemic sepsis with SOFA-Score between 3 and 17 points. The mortality rate was 40%. Significant differences between surviving and deceased patients were shown by PCT, INR and aPTT (p < 0.05). CONCLUSION: Severe Fournier's gangrene continues to be a major challenge with a high mortality rate. Only rapid diagnosis, urgent extensive surgical debridement and intensive care therapy can lead to a favourable outcome in these critically ill patients. Vacuum-assisted closure can be successfully used in the management of soft-tissue defects.

Status quo of the use of DCS concepts and outcome with focus on blunt abdominal trauma : A registry-based analysis from the TraumaRegister DGU®.

INTRODUCTION: Damage control surgery (DCS) is a standardized treatment concept in severe abdominal injury. Despite its evident advantages, DCS bears the risk of substantial morbidity and mortality, due to open abdomen therapy (OAT). Thus, identifying the suitable patients for that approach is of utmost importance. Furthermore, little is known about the use of DCS and the related outcome, especially in blunt abdominal trauma. METHODS: Patients recorded in the TraumaRegister DGU® from 2008 to 2017, and with an Injury Severity Score (ISS) ≥ 9 and an abdominal injury with an Abbreviated Injury Scale (AIS) score ≥ 3 were included in that registry-based analysis. Patients with DCS and temporary abdominal closure (TAC) were compared with patients who were treated with a laparotomy and primary closure (non-DCS) and those who did receive non-operative management (NOM). Following descriptive analysis, a matched-pairs study was conducted to evaluate differences and outcomes between DCS and non-DCS group. Matching criteria were age, abdominal trauma severity, and hemodynamical instability at the scene. RESULTS: The injury mechanism was predominantly blunt (87.1%). Of the 8226 patients included, 2351 received NOM, 5011 underwent laparotomy and primary abdominal closure (non-DCS), and 864 were managed with DCS. Thus, 785 patient pairs were analysed. The rate of hepatic injuries AIS > 3 differed between the groups (DCS 50.3% vs. non-DCS 18.1%). DCS patients had a higher ISS (p = 0.023), required more significant volumes of fluids, more catecholamines, and transfusions (p < 0.001). More DCS patients were in shock at the accident scene (p = 0.022). DCS patients had a higher number of severe hepatic (AIS score ≥ 3) and gastrointestinal injuries and more vascular injuries. Most severe abdominal injuries in non-DCS patients were splenic injuries (AIS, 4 and 5) (52.1% versus 37.9%, p = 0.004). CONCLUSION: DCS is a strategy used in unstable trauma patients, severe hepatic, gastrointestinal, multiple abdominal injuries, and mass transfusions. The expected survival rates were achieved in such extreme trauma situations.

Recommendations on Postoperative Activities After Abdominal Operations and Incisional Hernia Repair-A National and International Survey.

Background: There is no conclusive data on postoperative recommendations after abdominal and hernia surgery, and there is significant variation in the literature on that question. Thus, this study evaluates the status quo of recommendations of postoperative activity restriction after abdominal surgery. Materials and Methods: A national (German) and international survey of general surgeons on postoperative recommendations after abdominal and hernia surgery was pooled and analyzed. Results: A total of 74.6% recommended postoperative reduced activity for 2 weeks or less after laparoscopy. For midline laparotomy, 48.8% considered a reduced activity of 4 weeks or less to be sufficient. A majority from the national survey recommended more than 4 weeks instead (60.2%), whereas only 31.5% from the international survey did so (p = 0.000). In the pooled analysis, 258 of 450 (57.3%) rated 4 weeks or less suitable. However, the recommendations differed significantly between the surveys (4 weeks or less: a national survey, 47.1% vs. international survey, 64.6%; p = 0.000). Conclusion: There was substantial variation in the given recommendations. However, we found no evidence against immediate mobilization, reduced physical activity, and lifting for up to 2 weeks after laparoscopic surgery and for up to 4 weeks after open abdominal surgery and open incisional/ventral hernia repair in uncomplicated and standard cases. There might be individual and socioeconomic benefits to allow patients to return to their whole personal level of activity and work without putting them at risk of complications. Due to lack of evidence, both retrospective and prospective, controlled studies are in need to develop reliable recommendations.

[The Impact of Lockdown during the COVID-19 Pandemic on Care for Elective Patients (C-elective Study) - Results of a Multicenter Survey]. / Die Auswirkung des Lockdowns während der COVID-19-Pandemie auf die Versorgung von elektiven Patienten (C-elective-Studie).

BACKGROUND: Due to the COVID-19-related lockdown regulations, surgical clinics had to cut down elective procedures. The impact of the cancellation and postponing surgery on patients is unclear. METHODS: All patients from six hospitals with canceled surgery during the first lockdown (03/16-04/24/2020) were asked to answer a questionnaire. RESULTS: In total, 225 patients took part. In 88 (39.1%) patients, the disease-related complaints changed, mainly towards an increase in severity (82.6%). That was especially true for hernia patients (44.4%). In 4% of the cases, there was a complication requiring surgery in the time interval between the original date of the operation and the interview. For about a third, the cancelation of scheduled surgery caused major administrative difficulties. Most of the patients (76.3%) understood the measures taken, though 40.4% of them considered that their indication was very urgent. DISCUSSION AND CONCLUSION: The overall complication rate was low, and patients agreed to the measures taken; however, especially hernia patients showed increasing symptoms and some acute incarcerations. It seems reasonable to monitor symptomatic patients closely, in order to prioritise them when surgical capacity is restricted.

Quality of Life After Open Abdominal Treatment With Vacuum-Assisted Wound Closure and Mesh-Mediated Fascial Traction.

INTRODUCTION: Little is known about the long-term outcome of open abdomen treatment with vacuum-assisted wound closure and mesh-3. Therefore, this study's purpose is to evaluate this with a particular focus on incisional hernia development and quality of life (QoL). MATERIALS AND METHODS: Fifty-five patients who underwent vacuum-assisted wound closure and mesh-mediated fascial traction at our institution from 2006 to 2013 were prospectively enrolled in this study. After a median follow-up period of 3.8 years, 34 patients attended a follow-up examination, including the SF-36 QoL questionnaire. RESULTS: The fascial closure rate was 74% (intention-to-treat) and 89% (per-protocol). Enteroatmospheric fistulae occurred in 1.8%. In-hospital mortality was 16.4%, and during the follow-up period, it was 27.4%. Incisional hernias developed in 35% of the cases.The SF-36 physical role (54.6 ± 41.0 (0-100), P < 0.01), physical functioning (68.4 ± 29.5 (0-100), P = 0.01), and physical component summary (41.6 ± 13.0 (19-62), P = 0.01) scores for the patient population were significantly lower than normative scores. The mental dimensions of QoL showed no differences.A subgroup analysis revealed that the lower scores for physical role, physical functioning, and physical component summary only existed in the subgroup of incisional hernia patients. In contrast, physical and mental SF-36 scores of patients without incisional hernias did not differ from the normative scores. CONCLUSIONS: Vacuum-assisted wound closure and mesh-mediated fascial traction seems to result in low complication rates. However, incisional hernias occur in 35%, which are the leading cause of reduced QoL. Measures to further improve this rate, such as prophylactic meshes, have to be evaluated.

The Significance of Visceral Protection in Preventing Enteroatmospheric Fistulae During Open Abdomen Treatment in Patients With Secondary Peritonitis: A Propensity Score-matched Case-control Analysis.

OBJECTIVE: To evaluate the influence of a visceral protective layer (VPL) on the formation of enteroatmospheric fistulae (EAF) in open abdomen treatment (OAT) for peritonitis. BACKGROUND: EAF formation is a severe complication of OAT. Despite the widespread use of OAT, there are no robust evidence-based recommendations for preventing EAF. METHODS: A total of 120 peritonitis patients with secondary peritonitis as a result of a perforation of a hollow viscus or anastomotic insufficiency who had undergone OAT were included, and 14 clinical parameters were recorded in prospective OAT databases at 2 tertiary referral centers. For this analysis, patients with a VPL were assigned to the treatment group and those without a VPL to the control group. Propensity Score (PS) matching was performed. Known risk factors in OAT such as malignant disease, mortality, emergency operation, OAT duration, and fascial closure were matching variables. The influence of VPL on EAF formation was statistically evaluated using logistic regression analysis. RESULTS: With 34 patients in each group, no notable differences were identified with regard to age, sex, underlying disease, mortality, emergency operation, fascial closure, and OAT duration. Overall, a mortality rate of 22.1% for OAT due to peritonitis was observed. Mean OAT duration was approximately 9 days, and secondary fascial closure was achieved in more than two-thirds of all patients. Fascial traction was used in more than 75% of cases. EAF formation was significantly more frequent in the control group (EAF formation: VPL group 2.9% vs control 26.5%; P = 0.00). In the final regression analysis, the use of VPL resulted in a significant reduction in the risk of EAF formation (odds ratio 0.08; 95% confidence interval 0.01-0.71, P = 0.02), which translates to a relative risk reduction of 89.1%. CONCLUSION: VPL effectively prevents EAF formation during OAT in patients with peritonitis. We recommend the consistent use of VPL as part of a standardized OAT treatment algorithm.

Lack of Standardized Advice on Physical Strain Following Abdominal Surgery.

BACKGROUND: In Germany as elsewhere, standardized recommendations are lacking on the avoidance of physical exertion to protect the abdom - inal wall in patients who have recently undergone abdominal surgery. It is unclear how much stress the abdominal wall can withstand and how long the patient should be exempted from work. The goal of this review is to determine whether there are any standardized, evidence-based recommendations for postoperative care from which valid recommendations for Germany can be derived. METHODS: We systematically searched the literature for evidence-based recommendations on exertion avoidance after abdominal surgery, as well as for information on the extent to which postoperative abdominal wall stress contributes to incisional hernia formation. We then created a questionnaire on recommendation practices and sent it to all of the chiefs of general and visceral surgery services that were listed in the German hospital registry (1078 chiefs of service as of June 2016). RESULTS: All 16 of the included studies on postoperative exertion avoidance contained low-level evidence that could only be used to formulate weak recommendations ("can," rather than "should" or "must"). Some 50 000 incisional hernia repair procedures are performed in Germany each year, with a reported incidence of 12.8% in the first two years after surgery. The scientifically documented risk factors for incisional herniation are related to techniques of wound closure, the suture materials used, wound infections, and the patient risk profile. From the biological point of view, the abdominal wall regains full, normal resistance to exertional stress 30 days after a laparotomy with uncomplicated healing. Most incisional hernias (>50%) arise 18 months or more after surgery; they are more common in patients who have avoided exertion for longer periods of time (more than 8 weeks). Our questionnaire was returned by 386 surgical clinics. The responses showed that 78% of recommendations were based on personal experience only. The recommendations varied widely; exertion avoidance was recommended for as long as 6 months. CONCLUSION: The dilemma of a deficient evidence base for postoperative exertion avoidance to protect the abdominal wall should be resolved with the much higher-quality evidence available from hernia research, which concerns the patient population with the biologically least favorable starting conditions. Based on our analysis of the available literature in light of the biomechanical principles of abdominal wall healing, we propose a new set of recommendations on postoperative exertion avoidance after abdominal surgery, with the goal of eliminating excessively protracted exertion avoidance and enabling a timely return to work.

Prophylactic Onlay Mesh Implantation During Definitive Fascial Closure After Open Abdomen Therapy (PROMOAT): Absorbable or Non-absorbable? Methodical Description and Results of a Feasibility Study.

Introduction: Incisional hernia development after open abdomen therapy (OAT) remains a common complication in the long run. To demonstrate the feasibility, we describe our method of prophylactic onlay mesh implantation with definitive fascial closure after open abdomen therapy (PROMOAT). To display the feasibility of this concept, we evaluated the short-term outcome after absorbable and non-absorbable synthetic mesh implantation as prophylactic onlay. Material and Methods: Ten patients were prospectively enrolled, and prophylactic onlay mesh (long-term absorbable or non-absorbable) was implanted at the definitive fascial closure operation. The cohort was followed up with a special focus on incisional hernia development and complications. Results: OAT duration was 21.0 ± 12.6 days (95% CI: 16.9-25.1). Definitive fascial closure was achieved in all cases. No incisional hernias were present during a follow-up interval of 12.4 ± 10.8 months (range 1-30 months). Two seromas and one infected hematoma occurred. The outcome did not differ between mesh types. Conclusion: The prophylactic onlay mesh implantation of alloplastic, long-term absorbable, or non-absorbable meshes in OAT showed promising results and only a few complications that were of minor concern. Incisional hernias did not occur during follow-up. To validate the feasibility and safety of prophylactic onlay mesh implantation long-term data and large-scaled prospective trials are needed to give recommendations on prophylactic onlay mesh implantation after OAT.

Correction: Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue.

[This corrects the article DOI: 10.1371/journal.pone.0145937.].

Clonal heterogeneity of FLT3-ITD detected by high-throughput amplicon sequencing correlates with adverse prognosis in acute myeloid leukemia.

In acute myeloid leukemia (AML), internal tandem duplications (ITDs) of FLT3 are frequent mutations associated with unfavorable prognosis. At diagnosis, the FLT3-ITD status is routinely assessed by fragment analysis, providing information about the length but not the position and sequence of the ITD. To overcome this limitation, we performed cDNA-based high-throughput amplicon sequencing (HTAS) in 250 FLT3-ITD positive AML patients, treated on German AML Cooperative Group (AMLCG) trials. FLT3-ITD status determined by routine diagnostics was confirmed by HTAS in 242 out of 250 patients (97%). The total number of ITDs detected by HTAS was higher than in routine diagnostics (n = 312 vs. n = 274). In particular, HTAS detected a higher number of ITDs per patient compared to fragment analysis, indicating higher sensitivity for subclonal ITDs. Patients with more than one ITD according to HTAS had a significantly shorter overall and relapse free survival. There was a close correlation between FLT3-ITD mRNA levels in fragment analysis and variant allele frequency in HTAS. However, the abundance of long ITDs (≥75nt) was underestimated by HTAS, as the size of the ITD affected the mappability of the corresponding sequence reads. In summary, this study demonstrates that HTAS is a feasible approach for FLT3-ITD detection in AML patients, delivering length, position, sequence and mutational burden of this alteration in a single assay with high sensitivity. Our findings provide insights into the clonal architecture of FLT3-ITD positive AML and have clinical implications.

Soft document clustering using a novel graph covering approach.

BACKGROUND: In text mining, document clustering describes the efforts to assign unstructured documents to clusters, which in turn usually refer to topics. Clustering is widely used in science for data retrieval and organisation. RESULTS: In this paper we present and discuss a novel graph-theoretical approach for document clustering and its application on a real-world data set. We will show that the well-known graph partition to stable sets or cliques can be generalized to pseudostable sets or pseudocliques. This allows to perform a soft clustering as well as a hard clustering. The software is freely available on GitHub. CONCLUSIONS: The presented integer linear programming as well as the greedy approach for this NP -complete problem lead to valuable results on random instances and some real-world data for different similarity measures. We could show that PS-Document Clustering is a remarkable approach to document clustering and opens the complete toolbox of graph theory to this field.