High-sensitive nascent transcript sequencing reveals BRD4-specific control of widespread enhancer and target gene transcription.

Gene transcription by RNA polymerase II (Pol II) is under control of promoters and distal regulatory elements known as enhancers. Enhancers are themselves transcribed by Pol II correlating with their activity. How enhancer transcription is regulated and coordinated with transcription at target genes has remained unclear. Here, we developed a high-sensitive native elongating transcript sequencing approach, called HiS-NET-seq, to provide an extended high-resolution view on transcription, especially at lowly transcribed regions such as enhancers. HiS-NET-seq uncovers new transcribed enhancers in human cells. A multi-omics analysis shows that genome-wide enhancer transcription depends on the BET family protein BRD4. Specifically, BRD4 co-localizes to enhancer and promoter-proximal gene regions, and is required for elongation activation at enhancers and their genes. BRD4 keeps a set of enhancers and genes in proximity through long-range contacts. From these studies BRD4 emerges as a general regulator of enhancer transcription that may link transcription at enhancers and genes.

Comparison of videolaryngoscopy and direct laryngoscopy by German paramedics during out-of-hospital cardiopulmonary resuscitation; an observational prospective study.

BACKGROUND: Videolaryngoscopy (VL) has become a popular method of intubation (ETI). Although VL may facilitate ETI in less-experienced rescuers there are limited data available concerning ETI performed by paramedics during CPR. The goal was to evaluate the impact VL compared with DL on intubation success and glottic view during CPR performed by German paramedics. We investigated in an observational prospective study the superiority of VL by paramedics during CPR compared with direct laryngoscopy (DL). METHODS: In a single Emergency Medical Service (EMS) in Germany with in total 32 ambulances paramedics underwent an initial instruction from in endotracheal intubation (ETI) with GlideScope® (GVL) during resuscitation. The primary endpoint was good visibility of the glottis (Cormack-Lehane grading 1/2), and the secondary endpoint was successful intubation comparing GVL and DL. RESULTS: In total n = 97 patients were included, n = 69 with DL (n = 85 intubation attempts) and n = 28 VL (n = 37 intubation attempts). Videolaryngoscopy resulted in a significantly improved visualization of the larynx compared with DL. In the group using GVL, 82% rated visualization of the glottis as CL 1&2 versus 55% in the DL group (p = 0.02). Despite better visualization of the larynx, there was no statistically significant difference in successful ETI between GVL and DL (GVL 75% vs. DL 68.1%, p = 0.63). CONCLUSIONS: We found no difference in Overall and First Pass Success (FPS) between GVL and DL during CPR by German paramedics despite better glottic visualization with GVL. Therefore, we conclude that education in VL should also focus on insertion of the endotracheal tube, considering the different procedures of GVL. TRIAL REGISTRATION: German Clinical Trial Register DRKS00020976, 27. February 2020 retrospectively registered.

[West Africa Ebola outbreak - immediate and hands-on formation: the pre-deployment training program for frontline aid workers of the German Red Cross, other aid organizations, and the German Armed Forces, Wuerzburg, Germany 2014/15]. / Ebolafieberepidemie in Westafrika ­ schnelle und praxisnahe Ausbildung: Das Vorbereitungstraining für Einsatzkräfte des Deutschen Roten Kreuzes, anderer Hilfsorganisationen und der Bundeswehr, Würzburg, 2014 und 2015.

BACKGROUND: In September 2014, the German government mandated the German Red Cross (GRC) and the German Armed Forces to support the international efforts to stop the epidemic of Ebola virus disease (EVD) in West-Africa. The GRC requested specific training from the Medical Mission Institute Wuerzburg (MI). OBJECTIVES: We describe and discuss the development, strategy, results, and evaluation of the program to formulate conclusions and recommendations for similar emergencies. METHODS: On 26 September 2014, it was agreed to establish a two-day training program to prepare Ebola aid workers for the treatment of EVD patients and infection protection in Ebola treatment centers (ETC) in the epidemic area. Course evaluation was based on protocoled discussions with participants and standardized questionnaires. RESULTS: The training started on 6 October 2014. By 24 February 2015, 214 trainees participated in 14 courses. Of 96 GRC staff deployed to West Africa, 90 (94%) participated in the training. Course content included containment strategy in filovirus outbreaks and practical exercises for standardized procedures in personal protective equipment (PPE). The average trainer-trainee ratio in PPE exercises was 1:3. "Excellent" or "good" ratings were received on 93% of the evaluations. CONCLUSION: Rapid implementation was possible by teaching a harmonized, and field-approved concept for infection protection and treatment. Realistic simulated scenarios and field-experienced trainers allowed transfer of knowledge as well as reassurance. Additional recommendations are further conversion of the training into a permanent program and, in the case of a crisis, interlocking of training with operational planning to allow rapid escalation and adaptation. Also, the concepts for training and interventions should be harmonized and developed further for additional challenges like airborne transmission and application of intensive-care medicine.

Feasibility and Impact of Focused Intraoperative Transthoracic Echocardiography on Management in Thoracic Surgery Patients: An Observational Study.

OBJECTIVES: Intraoperative focused transthoracic echocardiography (TTE) is feasible and has an effect on the management of hemodynamically unstable surgical patients. Furthermore, in noncardiac thoracic surgery, TTE might provide additional information for hemodynamic treatment. Transthoracic accessibility during thoracic surgical interventions is assumed to be difficult. For patients positioned on their right side, a modified subcostal transthoracic view might be helpful. DESIGN: A prospective observational study. SETTING: Single-center university hospital. PARTICIPANTS: The study comprised 105 consecutive patients undergoing noncardiac thoracic surgery. INTERVENTIONS: Focused TTE was performed during anesthetic induction after intubation for mechanical ventilation. Intraoperative focused TTE, after positioning and draping for surgery, was attempted again for all 105 patients. Changes in patient management due to the results of the TTE were documented and analyzed. MEASUREMENTS AND MAIN RESULTS: Presurgical TTE with mechanical ventilation was applied successfully in 98.1% of 105 patients. Intraoperative imaging was successful in 90 patients (85.7%). Results of intraoperative TTE led to the modification of perioperative management in 39 patients (37.1%), 20 (22.0%) of these during surgery. CONCLUSIONS: TTE in noncardiac thoracic surgery is feasible using a modified subcostal view and has an effect on hemodynamic management in a considerable number of patients.

School sport-associated injuries in adolescents: A single center experience.

BACKGROUND: Each year, on average 1.26 million students face physical injuries at German schools and universities. Implementation of systematic prevention programs against school-associated injuries in adolescents is poor. Part of the reason might be a lack of data on nature and frequency of common school-associated injuries. OBJECTIVE: The aim of this study was to obtain qualitative and quantitative data that might help to develop prevention or protection strategies against sport-associated injuries at school. METHODS: A retrospective analysis was conducted on all patients between the ages of 10 and 16 years admitted from January 1st, 2009 to December 31st, 2013 to the emergency room of an academic teaching hospital for school-associated injuries (n= 901). For injuries associated with school sports, time of injury, type of sports and injured body region were analyzed. RESULTS: A significant part of school-associated injuries occurred in school sports (55.7%). The frequency of school sport-associated injuries per school day did not differ between months or seasons of the school year. Most injuries occurred between the ages of thirteen to fifteen. Ball sports were associated with 41% of all sport-associated injuries, particularly with soccer (22%). Distal extremities like hands (38.4%) and feet/ankle (30.3%) were predominantly injured, but only 5% of cases needed surgery. CONCLUSIONS: Most school-associated injuries occur in school sport, particularly with ball sports. Mostly, distal extremities were injured. Implementation of systematic prevention strategies for a reduction in finger injuries should be subject of future research.

Recovery and prediction of postoperative muscle power - is it still a problem?

BACKGROUND: In the postoperative period, immediate recovery of muscular power is essential for patient safety, but this can be affected by anaesthetic drugs, opioids and neuromuscular blocking agents (NMBA). In this cohort study, we evaluated anaesthetic and patient-related factors contributing to reduced postoperative muscle power and pulse oximetric saturation. METHODS: We prospectively observed 615 patients scheduled for minor surgery. Premedication, general anaesthesia and respiratory settings were standardized according to standard operating procedures (SOP). If NMBAs were administered, neuromuscular monitoring was applied to establish a Train of four (TOF)-Ratio of >0.9 before extubation. After achieving a modified fast track score > 10 at 4 time points up to 2 h postoperatively, we measured pulse oximetric saturation and also static and dynamic muscle power, using a high precision digital force gauge. Loss of muscle power in relation to the individual preoperative baseline value was analysed in relation to patient and anaesthesia-related factors using the T-test, simple and multiple stepwise regression analysis. RESULTS: Despite having achieved a TOF ratio of >0.9 a decrease in postoperative muscle power was detectable in most patients and correlated with reduced postoperative pulse oximetric saturation. Independent contributing factors were use of neuromuscular blocking agents (p < 0.001), female gender (p = 0.001), TIVA (p = 0.018) and duration of anaesthesia >120 min (p = 0.019). CONCLUSION: Significant loss of muscle power and reduced pulse oximetric saturation are often present despite a TOF-Ratio > 0.9. Gender differences are also significant. A modified fast track score > 10 failed to predict recovery of muscle power in most patients. TRIAL REGISTRATION: German Clinical Trial Register DRKS-ID DRKS00006032 ; Registered: 2014/04/03.

Impact of Focused Intraoperative Transthoracic Echocardiography by Anesthesiologists on Management in Hemodynamically Unstable High-Risk Noncardiac Surgery Patients.

OBJECTIVES: Focused transthoracic echocardiography (TTE) is used perioperatively for surgical patients. Intraoperative application of TTE is feasible, but its benefits remain unclear. The intention of this study was to investigate the effect of intraoperative TTE on the management of high-risk noncardiac surgery patients. DESIGN: A prospective interventional study. SETTING: Single-center university hospital. PARTICIPANTS: Fifty consecutive hemodynamically unstable high-risk patients anesthetized for noncardiac surgery. INTERVENTIONS: Focused TTE was performed on hemodynamically unstable anesthetized patients whenever circulatory instability (defined as hypotension or low cardiac output) occurred intraoperatively. A cardiac output monitoring system using pulse contour analysis was established before induction of anesthesia. The intended therapy for stabilizing the patient was documented; however, the management actually administered was guided by the results of the TTE. Differences between the 2 lines of management were documented and analyzed. MEASUREMENTS AND MAIN RESULTS: Intraoperative TTE was applied successfully in all 50 unstable patients. In 33 patients (66%, 95% confidence interval, 52.11-77.61) TTE led to a change of management. Altogether, 82 episodes of hemodynamic instability were recorded, including 38 episodes (46.34%, 95% confidence interval, 35.95-57.06) in which TTE led to a change of treatment. The most common pathologic finding was hypovolemia (66%); in contrast, in 22%, right-heart overload or right-heart failure (4%) was detected. CONCLUSIONS: Focused TTE by anesthesiologists can provide new information that may alter the hemodynamic management of unstable high-risk noncardiac surgery patients in the operating room.

Implementation and effects of pulse-contour- automated SVV/CI guided goal directed fluid therapy algorithm for the routine management of pancreatic surgery patients.

BACKGROUND: Goal directed fluid management in major abdominal surgery has shown to reduce perioperative complications. The approach aims to optimize the intravascular fluid volume by use of minimally invasive devices which calculate flow-directed variables such as stroke volume (SV) and stroke volume variation (SVV). OBJECTIVE: We aimed to show the feasibility of routinely implementing this type of hemodynamic monitoring during pancreatic surgery, and to evaluate its effects in terms of perioperative fluid management and postoperative outcomes. METHODS: All patients undergoing pancreatic surgery at a university hospital during two successive 12 months periods were included in this retrospective cohort analysis. Twelve months after the implementation of a standard operating procedure for a goal directed therapy (GDT, N = 45) using a pulse contour automated hemodynamic device were compared with a similar period before its use (control, N = 31) regarding mortality, length of hospital and ICU stay, postoperative complications and the use of fluids and vasopressors. RESULTS: Overall, 76 patients were analysed. Significantly less crystalloids were used in the GDT group. Patients receiving GDT showed significantly fewer severe complications (insufficiency of intestinal anastomosis: 0 vs. 5 (P = 0.0053) and renal failure: 0 vs. 4 (P = 0.0133). Mortality for pancreatic surgery was 1 vs. 3 patients, (P = 0.142), and length of stay (LOS) in the intensive care unit (ICU) was 4.38 ± 3.63 vs. 6.87 ± 10.02 (P= 0.0964) days. Use of blood products was significantly less within the GDT group. CONCLUSIONS: Implementation of a SOP for a GDT in the daily routine using flow-related parameters is feasible and is associated with better outcomes in pancreatic surgery.

Improving Ebola infection prevention and control in primary healthcare facilities in Sierra Leone: a single-group pretest post-test, mixed-methods study.

BACKGROUND: Accomplishing infection prevention and control (IPC) in health facilities in Sub-Saharan Africa is challenging. Owing to poor IPC, healthcare workers (HCWs) were frequently infected during Sierra Leone's Ebola epidemic. In late 2014, IPC was rapidly and nationally scaled up. We carried out workshops in sampled facilities to further improve adherence to IPC. We investigated HCW experiences and observed practice gaps, before and after the workshops. METHODS: We conducted an uncontrolled, before and after, mixed-methods study in eight health facilities in Bo and Kenema Districts during December 2014 and January 2015. Quantitative methods administered to HCWs at baseline and follow-up included a survey on attitudes and self-efficacy towards IPC, and structured observations of behaviours. The intervention involved a workshop for HCWs to develop improvement plans for their facility. We analysed the changes between rounds in survey responses and behaviours. We used interviews to explore attitudes and self-efficacy throughout the study period. RESULTS: HCWs described IPC as 'life-saving' and personal protective equipment (PPE) as uncomfortable for providers and frightening for patients. At baseline, self-efficacy was high (median=4/strongly agree). Responses reflecting unfavourable attitudes were low for glove use (median=1/strongly disagree, IQR, 1-2) and PPE use with ill family members (median=1, IQR, 1-2), and mixed for PPE use with ill HCWs (median=2/disagree, IQR, 1-4). Observations demonstrated consistent glove reuse and poor HCW handwashing. The maintenance of distance (RR 1.09, 95% CI 1.02 to 1.16) and patient handwashing (RR 1.19, 95% CI 1.3 to 1.25) improved to >90%. CONCLUSIONS: We found favourable attitudes towards IPC and gaps in practice. Risk perceptions of HCWs and tendencies to ration PPE where chronic supply chain issues normally lead to PPE stock-outs may affect practice. As Sierra Leone's Ebola Recovery Strategy aims to make all facilities IPC compliant, socio-behavioural improvements and a secure supply chain are essential.

Ebola Virus Disease Outbreak in Isiro, Democratic Republic of the Congo, 2012: Signs and Symptoms, Management and Outcomes.

Data collected during the 2012 Ebola virus disease (EVD) epidemic in the Democratic Republic of the Congo were analysed for clinical signs, symptoms and case fatality of EVD caused by Bundibugyo virus (BDBV), establishment of differential diagnoses, description of medical treatment and evaluation of the quality of clinical documentation. In a quantitative observational prospective study, global epidemiological data from 52 patients (34 patients within the community, 18 patients treated in the Ebola Treatment Centre) were entered anonymously into a database, subsequently matched and analysed. Relevant findings include an over-representation of females among community EVD cases (85.3%) and of community EVD cases in the age group of 15-54 years (82.4%). All ETC patients had fever (55.6% of all 18 ETC patients during their hospital stay) or self-reported fever (88.2% upon admission) at some point of time during their illness. Major symptoms of ETC patients during hospital stay included asthenia (82.4%), anorexia (82.4%), myalgia (70.6%), sore throat/difficulty swallowing (70.6%), arthralgia (76.5%) and nausea (70.6%). Gastrointestinal signs and symptoms (nausea, diarrhoea, vomiting) (76.4%) as well as general pain (94.1%) were frequent in ETC patients. The median duration of EVD was 18 days, while the mean incubation period was 11.3 days. Differential diagnosis of EVD included malaria (28.3%), intestinal parasitosis (10.9%), and infectious syndrome (10.9%). There was also an important variation in clinical evolvement. Quality of documentation was adversely affected by the way patient file contents were transferred from inside to outside the high-risk zone, entailing a mean mismatch value of 27.3% between patient file contents inside vs. outside the high-risk zone. This study adds further description of EVD (frequently non-specific signs and symptoms, non frequent bleeding, a long incubation period, long duration of disease) and emphasizes the need for improving clinical monitoring and documentation in EVD outbreak settings.

Supplemental Interscalene Blockade to General Anesthesia for Shoulder Arthroscopy: Effects on Fast Track Capability, Analgesic Quality, and Lung Function.

BACKGROUND: After shoulder surgery performed in patients with interscalene nerve block (without general anesthesia), fast track capability and postoperative pain management in the PACU are improved compared with general anesthesia alone. However, it is not known if these evidence-based benefits still exist when the interscalene block is combined with general anesthesia. METHODS: We retrospectively analyzed a prospective cohort data set of 159 patients undergoing shoulder arthroscopy with general anesthesia alone (n = 60) or combined with an interscalene nerve block catheter (n = 99) for fast track capability time. Moreover, comparisons were made for VAS scores, analgesic consumption in the PACU, pain management, and lung function measurements. RESULTS: The groups did not differ in mean time to fast track capability (22 versus 22 min). Opioid consumption in PACU was significantly less in the interscalene group, who had significantly better VAS scores during PACU stay. Patients receiving interscalene blockade had a significantly impaired lung function postoperatively, although this did not affect postoperative recovery and had no impact on PACU times. CONCLUSION: The addition of interscalene block to general anesthesia for shoulder arthroscopy did not enhance fast track capability. Pain management and VAS scores were improved in the interscalene nerve block group.

Impact of regional femoral nerve block during general anesthesia for hip arthoplasty on blood pressure, heart rate and pain control: A randomized controlled study.

BACKGROUND: Adequate pain management is essential for preventing hemodynamic instability which can affect the perfusion of vital organs during the perioperative period, particularly in geriatric patients. For hip arthroplasty, peripheral nerve block is frequently used, limiting the adverse effects of opioid and non-opioid analgesics. OBJECTIVE: The aim was to survey the impact of a supplementary single shot femoral nerve block (FNB) on hemodynamic stability and pain level. METHODS: After registration at German Clinical Trial Register (DRKS-ID): DRKS00000752. and Ethics Committee approval (University Hospital of Marburg), 80 patients who underwent elective hip surgery were included. Half of them were randomly assigned to receive a FNB followed by general anesthesia; a control group received only general anesthesia as standard procedure (STD). Blood pressure and heart rate were measured and recorded every five minutes during surgery and stay at the postanesthesia care unit (PACU). RESULTS: Fifty-two patients were included for statistical analysis. The FNB group had significantly lower systolic blood pressures during and after surgery and lower diastolic blood pressure postoperatively, heart rate, as well as opioid and non-steroidal anti-inflammatory consumption. CONCLUSIONS: Femoral nerve block improved perioperative hemodynamic stability mostly likely attributable to an overall reduced sympathico adrenergic tone.

Perineural hematoma may result in nerve inflammation and myelin damage.

BACKGROUND AND OBJECTIVES: Perineural hematoma may occur during performance of peripheral nerve blocks. The aim of this study was to test the hypothesis that an iatrogenic hematoma in the immediate vicinity of a peripheral nerve may cause histologic evidence of nerve injury. METHODS: Fifty milliliters of autologous blood was injected adjacent to the right sciatic nerve in 20 anesthetized female pigs. In order to discern between blood-related volume and immune effects, 50 mL of albumin was injected at the same location in an additional 22 pigs. Either blood or albumin was injected in random order. The left sciatic nerve served as a negative control in all animals, that is, either no needle placement or needle placement without injection. After 48 hours, the nerves were resected. The grade of nerve injury was scored from 0 (no injury) to 3 (severe injury) by histologic analysis of myelin tissue and inflammatory cells. RESULTS: Eighty-two nerve specimens were examined. Injury scores were significantly (P < 0.01) higher in the blood injection (n = 20; median [interquartile range] 2 [2-2]) and albumin injection (n = 22, 1 [1-2]) conditions compared with the no needle placement (n = 22, 0 [0-1]) and "dry needle placement" (n = 20, 1 [0-1]) conditions. Widespread inflammatory changes were seen in the blood injection group, in which 15% of nerve specimens showed damage to myelin. CONCLUSIONS: Our data suggest that hematoma adjacent to nerve tissue may result in structural nerve injury and inflammatory changes.

[Laser sheath extraction of an infected pacemaker lead]. / Extraktion einer infizierten Schrittmacherelektrode mittels Lasersheath.

A case of pacemaker electrode infection with Staphylococcus aureus is presented. In order to avoid sternotomy, the right ventricular pacemaker lead, which had been implanted for 15 years, was successfully extracted using a laser sheath despite large endocarditic vegetations on the pacemaker lead. After completion of a 6-week course of antibiotics, the patient was discharged without any further evidence of infection.

Re-admission to Level 2 unit after hip-fracture surgery - Risk factors, reasons and outcome.

INTRODUCTION: Hip fractures are common geriatric fractures with increasing incidence. Treatment of these fractures is still associated with high rates of complications and poor outcome. Data concerning unexpected re-admission to a Level 2 unit after an initial inconspicuous postoperative course are limited. We aimed to identify causes and associated risk factors for admission as well as impact of re-admission on acute care and short-term outcome. PATIENTS AND METHODS: Patients over 60 years of age with hip fractures were included in this prospective single-centre observational study. Patients with polytrauma or malignancy-associated fractures were excluded. Age, gender, fracture type, pre-fracture residential, physical and cognitive status, recording to the American Society of Anesthesiologists (ASA) score, Barthel Index (BI) and Mini-Mental State Examination (MMSE) were recorded on admission. Date, type of surgery and operation time were evaluated. Postoperatively, the prevalence of and reasons for unexpected re-admission to the Level 2 unit and patients' outcome were measured. Parameters were hospital mortality, BI at discharge, length of stay in hospital and type of discharge. Univariate and multivariate analyses were performed to identify risk factors for admission to the Level 2 unit and influence on patients' outcome. RESULTS: Out of 402 included patients, 48 (12%) were re-admitted to the Level 2 unit. The most frequent reasons were non-surgical (n=38), such as respiratory failure (n=12), cardiovascular diseases (n=8) and acute renal failure (n=5). Ten patients were re-admitted due to a revision surgery of the hip. We identified two independent risk factors for readmission: male gender (odds ratio (OR)=2.38, confidence interval (95% CI)=1.10-5.15, p=0.027) and type of fracture, especially femoral neck fracture (OR=7.40, 95% CI=2.39-23.26, p=0.001). Patients who were re-admitted to the Level 2 unit had a higher mortality (ß=2.09, OR=8.07, 95% CI=2.44-26.75, p=0.001), an increase in hospital stay (ß=7.0, 95% CI 5.2-8.7, p<0.001) and a lower functional outcome (BI, ß=-17, 95% CI=-23 to -10, p<0.001). CONCLUSION: Unexpected admission to the Level 2 unit in the post-surgical period is a frequent phenomenon in geriatric hip-fracture patients. Males and femoral neck fracture patients seem to be especially endangered. Although the majority of reasons for admissions were not immediately life-threatening illnesses, they had a substantial negative impact on patients' outcome. This emphasises the importance of careful handling of this frail patient population.