Myeloperoxidase enhances the migration and invasion of human choriocarcinoma JEG-3 cells.

Myeloperoxidase (MPO) is one of the most abundant proteins in neutrophil granules. It catalyzes the production of reactive oxygen species, which are important in inflammation and immune defense. MPO also binds to several proteins, lipids, and DNA to alter their function. MPO is present at the feto-maternal interface during pregnancy, where neutrophils are abundant. In this study, we determined the effect of MPO on JEG-3 human choriocarcinoma cells as a model of extravillous trophoblasts (EVTs) during early pregnancy. We found that MPO was internalized by JEG-3 cells and localized to the cytoplasm and nuclei. MPO internalization and activity enhanced JEG-3 cell migration and invasion, whereas this effect was impaired by pre-treating cells with heparin, to block cellular uptake, and MPO-activity inhibitor 4-ABAH. This study identifies a novel mechanism for the effect of MPO on EVT function during normal pregnancy and suggests a potential role of MPO in abnormal pregnancies.

The use of patient experience feedback in rehabilitation quality improvement and codesign activities: Scoping review of the literature.

OBJECTIVE: To characterize the literature, reported enablers, and gaps on the use of patient experience feedback for person-centered rehabilitation quality improvement and codesign activities. DESIGN: Scoping Review. DATA SOURCES: Scientific databases (PubMed, CINAHL, Rehabdata, Scopus, Web of Science, ProQuest), website searches (e.g. Beryl Institute), snowballing, and key-informant recommendations. METHODS: Two independent reviewers performed title and abstract screenings and full-text reviews. Eligibility focused on English-language, peer-reviewed (all time) and gray literature (last five years) that used patient experience feedback in rehabilitation improvement activities. The aims, settings, methods, findings, implications, and reported limitations were extracted, followed by content analyses identifying reported enablers and gaps. RESULTS: Among the 901 unique references and 52 full texts reviewed, ten were included: four used patient experience surveys for improving patient experiences; six used codesign methodologies to engage patient feedback in service improvement activities. Implementation enablers included securing managerial support, having a structured methodology and facilitator, using efficient processes, engaging staff experiences, and using appreciative inquiry. Reported study gaps included limited follow-up, low sample sizes, analytical limitations, lack of reported limitations, or narrow range of perspectives (e.g. not from people with severe impairments). CONCLUSION: Few examples of the use of patient experience feedback in quality improvement or codesign activities were found in the rehabilitation literature. Patient experience improvement activities relied exclusively on retrospective survey data, which were not combined with often more actionable forms (e.g. qualitative, real time) of patient experience feedback. Further research might consider design of activities that collect and use patient experience feedback for rehabilitation service improvements.

COVID-19 lungs in post-mortem computed tomography.

Post-mortem computed tomography (PMCT) is a rapid and noninvasive diagnostic tool for important contributions to the identification of pulmonary findings in the deceased with pneumonia, including cases of coronavirus disease 2019 (COVID-19). Although computed tomography (CT) shows a high sensitivity for pneumonia in living persons, it is relatively unspecific for COVID-19 pneumonia clinically. Typical CT findings for viral pneumonia therefore require confirmation by PCR tests (polymerase chain reaction tests), even if lung infections with severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) show characteristic patterns, most frequently ground glass opacities (GGO) and a combination of GGO and air space consolidations. In the consecutive autopsy series of SARS-CoV­2 deaths from Hamburg, Germany, the most frequent cause of death was and still is COVID-19 pneumonia. Typical findings were frequently found in the PMCT in SARS-CoV-2-associated deaths, which were taken into account when classifying the death as COVID-19.

Vaginal laceration leading to air embolism during consensual sexual intercourse.

Vaginal injuries with clinical complications apart from local bleeding following sexual intercourse are thought to be rare events that have recently fostered a discussion on the topic. We report a case of a vaginal laceration resulting in death caused by air embolism in a non-pregnant woman during consensual sexual intercourse with digital and penile penetration. Hysterectomy and a preexisting vaginal injury were additional risk factors present in this case. Besides case history and autopsy findings, histological examination of the vaginal lesion and postmortem computer tomography (PMCT) helped in diagnosing the cause of death and underlying pathophysiological mechanisms.

[Postmortem imaging of the lung in cases of COVID-19 deaths]. / Postmortale Bildgebung der Lunge bei COVID-19-Todesfällen.

CLINICAL/METHODOLOGICAL ISSUE: COVID-19 is a new viral disease that is associated with inflammatory pulmonary changes which can be detected in computed tomography (CT). So far postmortem CT (PMCT) has not been used as a screening instrument for the evaluation of deaths with and without autopsy. In this respect, its validity has to be proved in comparison to clinical-radiological experiences. STANDARD RADIOLOGICAL METHODS: Postmortem CT METHODICAL INNOVATIONS: So far, PMCT can be regarded as a methodological innovation that has not yet been sufficiently evaluated for pneumonia. PERFORMANCE: CT in clinical routine has a high sensitivity for pneumonia. However, to what extent postmortem artifacts are relevant to PMCT still has to be determined. ACHIEVEMENTS: There is still no standard procedure for the postmortem radiological diagnosis of COVID-19 disease. Despite postmortem artifacts, PMCT can provide valuable information about the presence of pneumonia with interstitial character, especially without autopsy. PRACTICAL RECOMMENDATIONS: PMCT is particularly useful in the assessment of suspected cases of COVID-19 pneumonia for morphological assessment in the context of monitoring deaths in the current pandemic situation.

Evidence for systematic autopsies in COVID-19 positive deceased: Case report of the first German investigated COVID-19 death.

Forensic medicine and pathology involve specific health risks, whereby health workers are dealing with microorganisms, cells or parasites, which are referred to as biological agents. Biological agents are divided into four categories according to § 3 of the Biological Agents Ordinance. The newly identified coronavirus, severe acute respiratory syndrome, coronavirus 2 (SARS-CoV-2) that has spread rapidly around the world is placed into category 3 of the Biological Agents Ordinance, meaning pathogens that can cause serious illnesses in humans and may pose a risk to workers. The Robert Koch Institute, the German government's central scientific institution in the field of biomedicine issued the announcement, that aerosol-producing measures (including autopsies) of SARS-CoV­2 infected bodies should be avoided, despite the fact that autopsies are an important source of understanding the pathomorphological course of new diseases. The first German case of death due to a proven SARS-CoV­2 infection is presented with global multifocal reticular consolidation in the post-mortem computed tomography (CT) scan, a macroscopic and microscopic viral pneumonia and viral RNA of SARS-CoV­2 in pharyngeal mucosa and lung tissue.

[The first COVID-19 hotspot in a retirement home in Hamburg]. / Der erste COVID-19-Hotspot in einer Hamburger Senioreneinrichtung: Präventionskonzept, Letalität und Obduktionsbefunde.

Background: Coronavirus disease 2019 (COVID-19), a disease caused by the new coronavirus (SARS-CoV-2), is a particular threat to old people. At the end of March 2020, the first and so far largest outbreak of the disease occurred in a retirement home in Hamburg. Methods: Analysis of procedures in dealing with a residential unit affected by SARS-CoV­2, accommodating a risk group of 60 seniors with dementia is presented as well as a detailed presentation of post-mortem examination results of all 8 deceased tested positive for SARS-CoV­2. Results: Out of 60 residents, 39 were infected by SARS-CoV­2. Due to preventive procedures it was possible to stop further spreading of the infection to other residential areas. In all 8 fatal cases, the autopsy diagnosis was death due to COVID-19. Autopsies revealed all COVID-19 patients to have a fatal (broncho)pneumonia and signs of relevant pre-existing cardiac, renal and pulmonary conditions in all cases. In 75% (n = 6) of the cases a fresh venous thrombosis was found. In 66.7% (n = 4) of the cases thrombotic events were combined with peripheral pulmonary artery thromboembolisms. Conclusion: The cohort of SARS-CoV­2 infected residents of a nursing home is characteristic for clinical and epidemiological features of the new coronavirus disease. Due to a centralized evaluation of all fatalities at the Institute of Legal Medicine in Hamburg, a detailed examination of all deceased positive for SARS-CoV­2 was possible. Thereby, increased case fatality rates of approximately 20% could in all cases be assigned to a relevant number of pre-existing comorbidities of multiple organ systems, which was consistent with the clinical data available.

Psychological factors outmatched morphological markers in predicting limitations in activities of daily living and participation in patients with lumbar stenosis.

BACKGROUND: Recent demographic changes have led to a large population of older adults, many of whom experience degenerative disc diseases. Degenerative lumbar spinal stenosis (DLSS) is associated with considerable discomfort and limitations in activities of daily living (ADL). Symptomatic DLSS is one of the most frequent indications for spinal surgery. The aim of this study was to identify sociodemographic variables, morphological markers, depression as well as fear of movement that predict ADL performance and participation in social life in patients with DLSS. METHODS: Sixty-seven patients with DLSS (mean age 62.5 years [11.7], 50.7% females) participated in the study. Predictor variables were age, gender, duration of disease, three morphological markers (severity of the lumbar stenosis, the number of affected segments and presence of spondylolisthesis) as well as self-reported depression and fear of movement. Dependent variables were pain interference with the performance of ADLs, ADLs and participation in social life. Correlations between predictor and dependent variables were calculated before stepwise, linear regression analyses. Only significant correlations were included in the linear regression analyses. RESULTS: Variance explained by the predictor variables ranged between 12% (R2 = .12; pain interference-physical) and 40% (R2 = .40; ADL requiring lower extremity functioning; participation). Depression and fear of movement were the most powerful predictors for all dependent variables. Among the morphological markers only stenosis severity contributed to the prediction of ADLs requiring lower extremity functioning. CONCLUSION: Depression and fear of movement were more important predictors of the execution of ADLs and participation in social life compared to morphological markers. Elevated depressive symptoms and fear of movement might indicate limited adaptation and coping regarding the disease and its consequences. Early monitoring of these predictors should therefore be conducted in every spine centre. Future studies should investigate whether psychological screening or a preoperative psychological consultation helps to avoid operations and enables better patient outcomes.

Post-mortem analysis of prescription opioids-A follow-up examination by LC-MS/MS with focus on fentanyl.

Our aim was to investigate the reason for relatively low detection rates for opioids and fentanyl in particular in post-mortem cases in the State of Hamburg. We re-analysed 822 blood samples from two different time periods, 2011/12 and 2016. These samples had been previously analysed in accordance with post-mortem routine by a case selected strategy. All samples were re-analysed with an LC-MS/MS method specific for prescription opioids. The main point in the evaluation was to determine whether the previous analysis strategy had led to underreporting of drug-related deaths (DRD), especially with regard to fentanyl. Another aim was to evaluate changes in prescribing prevalence of opiates and opioids. We compared pharmacy claims data in Hamburg with Germany. The analyses showed that the number of DRD remained unaffected by the new analytical strategy. Detection rates in DRD, however, increased for fentanyl 3.4-fold from 1.2% to 4.1%, buprenorphine from 5.9% to 7.6%, oxycodone from 0% to 1.8%, tilidine from 1.8% to 2.4%. The most frequently detected opioids in DRD cases were methadone (39.4%) and heroin (20%). Prescription rates between 2011-2017 decreased in Hamburg for nearly all opioids, morphine by - 43.5%, buprenorphine - 43%, codeine - 57%, fentanyl - 25%, tilidine -17%, tramadol - 31%, and hydromorphone -6%. Oxycodone, tapentadol, and piritramide prescription rates increased. For Germany, a decrease in the prescription rates for fentanyl was also found during this period (-12.9 %), although not as pronounced as in Hamburg. Prescription rates for methadone were three to greater than five times higher in Hamburg as compared to the German average due to the higher number of substituted persons per inhabitant. Conclusion: Despite the global problem of opioid abuse, there are significant regional differences in the nature and extent of opioid abuse. It is necessary to collect data at the national level to develop appropriate prevention strategies.

Preferences for physical activity: a conjoint analysis involving people with chronic knee pain.

OBJECTIVE: To investigate individual preferences for physical activity (PA) attributes in adults with chronic knee pain, to identify clusters of individuals with similar preferences, and to identify whether individuals in these clusters differ by their demographic and health characteristics. DESIGN: An adaptive conjoint analysis (ACA) was conducted using the Potentially All Pairwise RanKings of all possible Alternatives (PAPRIKA) method to determine preference weights representing the relative importance of six PA attributes. Cluster analysis was performed to identify clusters of participants with similar weights. Chi-square and ANOVA were used to assess differences in individual characteristics by cluster. Multinomial logistic regression was used to assess associations between individual characteristics and cluster assignment. RESULTS: The study sample included 146 participants; mean age 65, 72% female, 47% white, non-Hispanic. The six attributes (mean weights in parentheses) are: health benefit (0.26), enjoyment (0.24), convenience (0.16), financial cost (0.13), effort (0.11) and time cost (0.10). Three clusters were identified: Cluster 1 (n = 33): for whom enjoyment (0.35) is twice as important as health benefit; Cluster 2 (n = 63): for whom health benefit (0.38) is most important; and Cluster 3 (n = 50): for whom cost (0.18), effort (0.18), health benefit (0.17) and enjoyment (0.18) are equally important. Cluster 1 was healthiest, Cluster 2 most self-efficacious, and Cluster 3 was in poorest health. CONCLUSIONS: Patients with chronic knee pain have preferences for PA that can be distinguished effectively using ACA methods. Adults with chronic knee pain, clustered by PA preferences, share distinguishing characteristics. Understanding preferences may help clinicians and researchers to better tailor PA interventions.

Mass poisoning with NPS: 2C-E and Bromo-DragonFly.

BACKGROUND: Reports of intoxications with new psychoactive substances (NPS) mostly involve young people, as they are the main consumers of these types of drugs. This report centers on a case that was unusual due to it being a mass-poisoning event involving middle-aged individuals who had consumed a combination of the two different new psychoactive drugs 2,5-dimethoxy-4-ethylphenethylamine (2C-E) and 1-(8-bromofuro[2,3-f][1]benzofuran-4-yl)-2-propanamine (Bromo-DragonFly, BDF). CASE HISTORY: The mass poisoning of 29 individuals (24-56 years old) resulted in their admission to six different hospitals with severe symptoms of intoxication. All symptoms manifested after consumption of an unknown drug formulation around lunchtime during an esoteric weekend seminar. INVESTIGATION: Urine (n = 11) and blood samples (n = 29), collected from the 29 individuals for police investigation, were analyzed with immunochemical techniques, GC/MS and LC-MS/MS. 2C-E was confirmed in seven urine samples, but not in blood. BDF was confirmed in all urine samples, and in 17 blood samples. The blood samples exhibited BDF concentrations between ca. 0.6 and ca. 2.0 µg/L, while urine concentrations of BDF ranged from ca. 1.6 to 35 µg/L. The concentration of 2C-E in urine was found to be between ca. 1.5 and 183 µg/L. All patients made a complete recovery, although some had required mechanical ventilation. CONCLUSION: The investigation and the presentation of this case illustrates not only mass intoxication with 2C-E and BDF, with corresponding blood and urine concentrations, but also the necessity of collecting urine samples in cases where NPS-consumption is suspected, in order to improve the chances of analytical detection.

Correction to: Mass poisoning with NPS: 2C-E and Bromo-DragonFly.

The original version of this article contains an error. The Author S. Lehmann incorrectly listed as S. Lehman. The correct spelling is presented above. The original article has been corrected.

Prospective study of device-related complications in intensive care unit detected by virtual autopsy.

BACKGROUND: There has been increasing use of invasive techniques, such as extracorporeal organ support, in intensive care units (ICU), and declining autopsy rates. Thus, new measures are needed to maintain high-quality standards. We investigated the potential of computed tomography (CT)-based virtual autopsy to substitute for medical autopsy in this setting. METHODS: We investigated the potential of virtual autopsy by post-mortem CT to identify complications associated with medical devices in a prospective study of patients who had died in the ICU. Clinical records were reviewed to determine the number and types of medical devices used, and findings from medical and virtual autopsies, related and unrelated to the medical devices, were compared. RESULTS: Medical and virtual autopsies could be performed in 61 patients (Group M/V), and virtual autopsy only in 101 patients (Group V). In Group M/V, 41 device-related complications and 30 device malpositions were identified, but only with a low inter-method agreement. Major findings unrelated to a device were identified in about 25% of patients with a high level of agreement between methods. In Group V, 8 device complications and 36 device malpositions were identified. CONCLUSIONS: Device-related complications are frequent in ICU patients. Virtual and medical autopsies showed clear differences in the detection of complications and device malpositions. Both methods should supplement each other rather than one alone for quality control of medical devices in the ICU. Further studies should focus on the identification of special patient populations in which virtual autopsy might be of particular benefit. CLINICAL TRIAL REGISTRATION: NCT01541982.

The AP-1 transcription factor FOSL1 causes melanocyte reprogramming and transformation.

The MAPK pathway is activated in the majority of melanomas and is the target of therapeutic approaches. Under normal conditions, it initiates the so-called immediate early response, which encompasses the transient transcription of several genes belonging to the AP-1 transcription factor family. Under pathological conditions, such as continuous MAPK pathway overactivation due to oncogenic alterations occurring in melanoma, these genes are constitutively expressed. The consequences of a permanent expression of these genes are largely unknown. Here, we show that FOSL1 is the main immediate early AP-1 member induced by melanoma oncogenes. We first examined its role in established melanoma cells. We found that FOSL1 is involved in melanoma cell migration as well as cell proliferation and anoikis-independent growth, which is mediated by the gene product of its target gene HMGA1, encoding a multipotent chromatin modifier. As FOSL1 expression is increased in patient melanoma samples compared to nevi, we investigated the effect of enhanced FOSL1 expression on melanocytes. Intriguingly, we found that FOSL1 acts oncogenic and transforms melanocytes, enabling subcutaneous tumor growth in vivo. During the process of transformation, FOSL1 reprogrammed the melanocytes and downregulated MITF in a HMGA1-dependent manner. At the same time, AXL was upregulated, leading to a shift in the MITF/AXL balance. Furthermore, FOSL1 re-enforced pro-tumorigenic transcription factors MYC, E2F3 and AP-1. Together, this led to the enhancement of several growth-promoting processes, such as ribosome biogenesis, cellular detachment and pyrimidine metabolism. Overall, we demonstrate that FOSL1 is a novel reprogramming factor for melanocytes with potent tumor transformation potential.

Validation of the NIH Toolbox in Individuals with Neurologic Disorders.

OBJECTIVE: Individuals with spinal cord injury (SCI), traumatic brain injury (TBI), and stroke experience a variety of neurologically related deficits across multiple domains of function. The NIH Toolbox for the Assessment of Neurological and Behavioral Function (NIHTB) examines motor, sensation, cognition, and emotional functioning. The purpose of this paper is to establish the validity of the NIHTB in individuals with neurologic conditions. METHODS: Community-dwelling individuals with SCI (n = 209), TBI (n = 184), or stroke (n = 211) completed the NIHTB. Relative risks for impaired performance were examined relative to a matched control groups. RESULTS: The largest group differences were observed on the Motor domain and for the Fluid Cognition measures. All groups were at increased risk for motor impairment relative to normative standards and matched controls. Fluid cognitive abilities varied across groups such that individuals with stroke and TBI performed more poorly than individuals with SCI; increased relative risks for impaired fluid cognition were seen for individuals in the stroke and TBI groups, but not for those in the SCI group. All three neurologic groups performed normally on most measures in the Sensation Battery, although TBI participants evidenced increased risk for impaired odor identification and the stroke group showed more vision difficulties. On the Emotion Battery, participants in all three groups showed comparably poor psychological well-being, social satisfaction, and self-efficacy, whereas the TBI group also evidenced slightly increased negative affect. CONCLUSIONS: Data provide support for the validity of the NIHTB in individuals with neurologic conditions.

Beyond the BRAFV600E hotspot: biology and clinical implications of rare BRAF gene mutations in melanoma patients.

BRAF gene mutations can be found in approximately 50% of melanomas, but the most common BRAF mutation leads to substitution at residue 600 of the protein, from valine to glutamic acid. BRAFV600E occurs in up to 95% of all melanoma cases and can be successfully blocked by using a combination of BRAF- and MEK inhibitors. The wider availability of next-generation sequencing is revealing more non-V600 BRAF mutations, and the clinical implications of these mutations are widely unknown. In this review, we will discuss the biology of the MAPK pathway and the different types of BRAF mutations as well as their effect on MEK activation. Current literature will be reviewed including in vitro data, case reports and case series.

Accuracy of Latarjet graft and screw position after using novel drill guide.

PURPOSE: For the success of Latarjet procedure a correct graft positioning is mandatory. Furthermore, the correct screw placement is important to avoid cartilage damage and soft tissue irritation. Due to a cadaveric experimental study, the accuracy of graft and screw positioning utilizing a novel drill guide for a minimal-invasive Latarjet procedure was analyzed. METHODS: Five human fresh-frozen shoulder specimens have been treated in accordance with the Congruent-Arc Latarjet technique using the glenoid bone loss set (Arthrex, Naples, FL, USA) with 3.75 mm cannulated screws throughout a 5 cm skin incision without detachment of the scapularis tendon. All procedures were performed by one single, experienced shoulder surgeon. The accuracy of graft and screw positioning was assessed due to a CT scan. RESULTS: A noticeable learning curve was noted during the study period as the first surgery took 45 min and the last 33 min. All grafts were correctly positioned with regard to the articular line of the glenoid surface. Impingement with the maximum head circumference was not encountered. The screw positions did not affect the suprascapular nerve. A damage of the graft was not noticed. CONCLUSIONS: The authors can recommend the usage of the new drill guide tested in this study. It seems to be beneficial in the Latarjet procedure and may ease correct graft positioning and prevent screw misplacement. Compared to fully arthroscopically performed Latarjet procedures it provides much steeper learning curve and seems technically easier and quicker to handle.

Validation and clinical utility of the executive function performance test in persons with traumatic brain injury.

This study examined the relationships between the Executive Function Performance Test (EFPT), the NIH Toolbox Cognitive Function tests, and neuropsychological executive function measures in 182 persons with traumatic brain injury (TBI) and 46 controls to evaluate construct, discriminant, and predictive validity. Construct validity: There were moderate correlations between the EFPT and the NIH Toolbox Crystallized (r = -.479), Fluid Tests (r = -.420), and Total Composite Scores (r = -.496). Discriminant validity: Significant differences were found in the EFPT total and sequence scores across control, complicated mild/moderate, and severe TBI groups. We found differences in the organisation score between control and severe, and between mild and severe TBI groups. Both TBI groups had significantly lower scores in safety and judgement than controls. Compared to the controls, the severe TBI group demonstrated significantly lower performance on all instrumental activities of daily living (IADL) tasks. Compared to the mild TBI group, the controls performed better on the medication task, the severe TBI group performed worse in the cooking and telephone tasks. Predictive validity: The EFPT predicted the self-perception of independence measured by the TBI-QOL (beta = -0.49, p < .001) for the severe TBI group. Overall, these data support the validity of the EFPT for use in individuals with TBI.