Search

The authors present the case of a 58-year-old man found hanging from a radiator by his shoelaces. The time of death was approximately 6 h before the body was discovered. An autopsy was performed approximately 24 h after the body was found, which revealed hemorrhages in the thoracic aorta at the junctions of the posterior intercostal arteries. Before autopsy, a routine whole-body CT scan was performed. Histologic examination of the aorta and the posterior intercostal arteries revealed a fresh hemorrhage into the tunica adventitia of the aorta. To our knowledge, there is no case description of such findings in hanged persons in the literature. Conclusion: Hemorrhages into the tunica adventitia of the junction of the posterior costal arteries may occur in association with suicidal hanging. The significance of these hemorrhages as a sign of vitality may be debated. [ABSTRACT FROM AUTHOR]

With the approval of the first two substances for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration (AMD), a standardized monitoring of patients treated with complement inhibitors in clinical practice is needed. Optical coherence tomography (OCT) provides high-resolution access to the retinal pigment epithelium (RPE) and neurosensory layers, such as the ellipsoid zone (EZ), which further enhances the understanding of disease progression and therapeutic effects in GA compared to conventional fundus autofluorescence (FAF). In addition, artificial intelligence-based methodology allows the identification and quantification of GA-related pathology on OCT in an objective and standardized manner. The purpose of this study was to comprehensively evaluate automated OCT monitoring for GA compared to reading center-based manual FAF measurements in the largest successful phase 3 clinical trial data of complement inhibitor therapy to date. Automated OCT analysis of RPE loss showed a high and consistent correlation to manual GA measurements on conventional FAF. EZ loss on OCT was generally larger than areas of RPE loss, supporting the hypothesis that EZ loss exceeds underlying RPE loss as a fundamental pathophysiology in GA progression. Automated OCT analysis is well suited to monitor disease progression in GA patients treated in clinical practice and clinical trials. [ABSTRACT FROM AUTHOR]

Neuraminic acid synthases are an important yet underexplored group of enzymes. Thus, in this research, we performed a detailed kinetic and stability analysis and a comparison of previously known neuraminic acid synthase from Neisseria meningitidis, and a novel enzyme, PNH5, obtained from a metagenomic library. A systematic analysis revealed a high level of similarity of PNH5 to other known neuraminic acid synthases, except for its pH optimum, which was found to be at 5.5 for the novel enzyme. This is the first reported enzyme from this family that prefers an acidic pH value. The effect of different metal cofactors on enzyme activity, i.e. Co2+, Mn2+ and Mg2+, was studied systematically. The kinetics of neuraminic acid synthesis was completely elucidated, and an appropriate kinetic model was proposed. Enzyme stability study revealed that the purified enzyme exhibits changes in its structure during time as observed by differential light scattering, which cause a drop in its activity and protein concentration. The operational enzyme stability for the neuraminic acid synthase from N. meningitidis is excellent, where no activity drop was observed during the batch reactor experiments. In the case of PNH5, some activity drop was observed at higher concentration of substrates. The obtained results present a solid platform for the future application of these enzymes in the synthesis of sialic acids. Key points: • A novel neuraminic acid synthase was characterized. • The effect of cofactors on NeuS activity was elucidated. • Kinetic and stability characterization of two neuraminic acid synthases was performed. [ABSTRACT FROM AUTHOR]

Objective: To assess the accuracy of CT and MRI reports of alert patients presenting after non-self-inflicted strangulation (NSIS) and evaluate the appropriateness of these imaging modalities in NSIS. Material and methods: The study was a retrospective analysis of patient characteristics and strangulation details, with a comparison of original radiology reports (ORR) to expert read-outs (EXR) of CT and MRI studies of all NSIS cases seen from 2008 to 2020 at a single centre. Results: The study included 116 patients (71% women, p <.001, χ2), with an average age of 33.8 years, mostly presenting after manual strangulation (97%). Most had experienced intimate partner violence (74% of women, p <.001, χ2) or assault by unknown offender (88% of men, p < 0.002 χ2). Overall, 132 imaging studies (67 CT, 51% and 65 MRI, 49%) were reviewed. Potentially dangerous injuries were present in 7%, minor injuries in 22%, and no injuries in 71% of patients. Sensitivity and specificity of ORR were 78% and 97% for MRI and 30% and 98% for CT. Discrepancies between ORR and EXR occurred in 18% of all patients, or 62% of injured patients, with a substantial number of unreported injuries on CT. Conclusions: The results indicate that MRI is more appropriate than CT for alert patients presenting after non-self-inflicted strangulation and underline the need for radiologists with specialist knowledge to report these cases in order to add value to both patient care and potential future medico-legal investigations. Clinical relevance statement: MRI should be preferred over CT for the investigation of strangulation related injuries in alert patients because MRI has a higher accuracy than CT and does not expose this usually young patient population to ionizing radiation. Key Points: • Patients presenting after strangulation are often young women with a history of intimate partner violence while men typically present after assault by an unknown offender. • Expert read-outs of CT and MRI revealed potentially dangerous injuries in one of 14 patients. • MRI has a significantly higher sensitivity than CT and appears to be more appropriate for the diagnostic workup of alert patients after strangulation. [ABSTRACT FROM AUTHOR]

The AGFAD (Arbeitsgemeinschaft für Forensische Alterdiagnostik, Study Group on Forensic Age Diagnostics) has published several recommendations regarding both technical aspects of computed tomography (CT) of the medial clavicular epiphysis (MCE) and the process of reading and interpreting the CT images for forensic age estimations (FAE). There are, however, no published recommendations regarding CT scan protocols and no dose reference values for CT of the MCE. The objective of this analysis was to assess adherence to AGFAD recommendations among practitioners of FAE and analyse reported dose-relevant CT scan parameters with the objective of helping to establish evidence-based dose reference values for FAE. A systematic literature search was conducted in PubMed and in Google Scholar with specific MeSH terms to identify original research articles on FAE with CT of the MCE from 1997 to 2022. A total of 48 studies were included. Adherence to AGFAD recommendations among practitioners of FAE is high regarding the use of Schmeling main stages (93%), bone window (79%), ≤ 1 mm CT slices (67%), axial/coronal CT images (65%), and Kellinghaus sub-stages (59%). The reporting of CT technique and CT dose-relevant scan parameters is heterogeneous and often incomplete in the current literature. Considering the success achieved by the AGFAD in creating standards of practice of FAE in living subjects, there is potential for the AGFAD to establish standards for radiation protection in FAE as well. [ABSTRACT FROM AUTHOR]

Copyright of Die Ophthalmologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Geographic atrophy (GA) represents a late stage of age-related macular degeneration, which leads to irreversible vision loss. With the first successful therapeutic approach, namely complement inhibition, huge numbers of patients will have to be monitored regularly. Given these perspectives, a strong need for automated GA segmentation has evolved. The main purpose of this study was the clinical validation of an artificial intelligence (AI)-based algorithm to segment a topographic 2D GA area on a 3D optical coherence tomography (OCT) volume, and to evaluate its potential for AI-based monitoring of GA progression under complement-targeted treatment. 100 GA patients from routine clinical care at the Medical University of Vienna for internal validation and 113 patients from the FILLY phase 2 clinical trial for external validation were included. Mean Dice Similarity Coefficient (DSC) was 0.86 ± 0.12 and 0.91 ± 0.05 for total GA area on the internal and external validation, respectively. Mean DSC for the GA growth area at month 12 on the external test set was 0.46 ± 0.16. Importantly, the automated segmentation by the algorithm corresponded to the outcome of the original FILLY trial measured manually on fundus autofluorescence. The proposed AI approach can reliably segment GA area on OCT with high accuracy. The availability of such tools represents an important step towards AI-based monitoring of GA progression under treatment on OCT for clinical management as well as regulatory trials. [ABSTRACT FROM AUTHOR]

Aim: This European multicentric study aimed to prove safety and performance of the Bonebridge BCI 602 in children and adults suffering from either conductive hearing loss (CHL), mixed hearing loss (MHL), or single-sided sensorineural deafness (SSD). Methods: 33 patients (13 adults and 10 children with either CHL or MHL and 10 patients with SSD) in three study groups were included. Patients were their own controls (single-subject repeated measures), comparing the unaided or pre-operative to the 3-month post-operative outcomes. Performance was evaluated by sound field thresholds (SF), word recognition scores (WRS) and/or speech reception thresholds in quiet (SRT) and in noise (SNR). Safety was demonstrated with a device-specific surgical questionnaire, adverse event reporting and stable pure-tone measurements. Results: The Bonebridge BCI 602 significantly improved SF thresholds (+ 25.5 dB CHL/MHL/SSD), speech intelligibility in WRS (+ 68.0% CHL/MHL) and SRT in quiet (− 16.5 dB C/MHL) and in noise (− 3.51 dB SNR SSD). Air conduction (AC) and bone conduction (BC) thresholds remained stable over time. All adverse events were resolved, with none unanticipated. Mean audio processor wearing times in hours [h] per day for the CHL/MHL group were ~ 13 h for adults, ~ 11 h for paediatrics and ~ 6 h for the SSD group. The average surgical length was 57 min for the CHL/MHL group and 42 min for the SSD group. The versatility of the BCI 602 (reduced drilling depth and ability to bend the transition for optimal placement) allows for treatment of normal, pre-operated and malformed anatomies. All audiological endpoints were reached. Conclusions: The Bonebridge BCI 602 significantly improved hearing thresholds and speech understanding. Since implant placement follows the patient's anatomy instead of the shape of the device and the duration of surgery is shorter than with its predecessor, implantation is easier with the BCI 602. Performance and safety were proven for adults and children as well as for the CHL/MHL and SSD indications 3 months post-operatively. [ABSTRACT FROM AUTHOR]

Purpose: The objective of the study was to evaluate the proposed cochlear duct length estimation based on the cochlear 'A value'. Furthermore, we assessed the interobserver variability between radiology and otolaryngology attending physicians and otolaryngology trainees. Methods: Thirteen pediatric cochlear implant candidates were retrospectively analyzed by three otolaryngology physicians (attending physician, second year, and fourth year trainees) and a radiology attending. The cochlear duct length was calculated based on the formula of Grover et al. The differences in acquired measurements between observers were compared using the Wilcoxon matched signed-rank test. Results: The differences in measurements between the attending otolaryngologist and radiologist were not statistically different, while several significant differences were observed with regard to measurements of attending doctors compared to both residents. In particular, a significant difference between the second year otolaryngology resident and otolaryngology and radiology attending was observed for one side (right ear p = 0.034 and p = 0.012, respectively). Moreover, the fourth year resident calculated significantly different cochlear duct measurements when compared to the attending otolaryngologist (left ear p = 0.014) and radiologist (right ear p = 0.047). Interestingly, differently experienced otolaryngology residents provided significantly different measurements for both ears. Conclusions: Based on these results, cochlear duct length measurement according to the proposed method may be a reliable and cost-effective method. Indeed, otolaryngology training may be sufficient to provide measurements comparable to radiologists. On the other hand, additional efforts should be invested during otolaryngology training in terms of the evaluation of radiological imaging which may increase the capabilities of otolaryngology residents in this regard. [ABSTRACT FROM AUTHOR]

A time span of 60 years covers the detection of catecholamines in the brain, their function in movement and correlation to Parkinson's disease (PD). The clinical findings that orally given l-DOPA can alleviate or even prevent akinesia gave great hope for the treatment of PD. Attention focused on the role of tyrosine hydroxylase (TH) as the rate-limiting enzyme in the formation of catecholamines. It became evident that the enzyme driven formation is lowered in PD. Such results could only be obtained from studying human brain samples demonstrating the necessity for human brain banks. Originally, a TH enzyme deficiency was suspected in PD. Studies were conducted on the enzyme properties: its induction and turnover, the complex regulation starting with cofactor requirements as tetrahydrobiopterin and ferrous iron, and the necessity for phosphorylation for activity as well as inhibition by toxins or regulatory feedback inhibition by catecholamines. In the course of time, it became evident that neurodegeneration and cell death of dopaminergic neurons is the actual pathological process and the decrease of TH a cophenomenon. Nevertheless, TH immunochemistry has ever since been a valuable tool to study neuronal pathways, neurodegeneration in various animal models of neurotoxicity and cell cultures, which have been used as well to test potential neuroprotective strategies. [ABSTRACT FROM AUTHOR]

Acknowledging previous reports with abnormal findings in sensory nerve conduction studies in up to 20% of patients with ALS [[6]] and earlier morphological findings in sensory nerve biopsies suggesting loss of sensory root ganglion neurons [[7]], an involvement of pathological I RFC1 i expansions as additional monogenic form or at least genetic risk factor for ALS might be discussed. However, one must admit, that we cannot differentiate an association of pathological I RFC1 i expansions with a combined phenotype of ALS and sensory neuro(no)pathy in our patient from a bare coincidence of ALS with a beginning CANVAS phenotype due to I RFC1 i pathology. In conclusion, the presented case with a concomitant sensory neuro(no)pathy and proven I RFC1 i expansion in addition to ALS should prompt a more systematical search for I RFC1 i expansion in larger patient cohorts with ALS and unexplained sensory involvement in order to disentangle a possible role of I RFC1 i pathology in ALS. [Extracted from the article]

In mass spectrometry-based proteomics, heavy internal standards are used to validate target peptide detections and to calibrate peptide quantitation. Here, we report light contamination present in heavy labelled synthetic peptides of high isotopic enrichment. Application of such peptides as assay-internal standards potentially compromises the detection and quantitation especially of low abundant cellular peptides. Therefore, it is important to adopt guidelines to prevent false-positive identifications of endogenous light peptides as well as errors in their quantitation from biological samples. [ABSTRACT FROM AUTHOR]

Copyright of Der Unfallchirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: The safety of first-line (1L) durvalumab in patients with advanced nonsmall-cell lung cancer (NSCLC) and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 (PS2) is unknown. This is an interim unplanned safety analysis of the study SAKK 19/17 for patients with metastatic NSCLC with programmed death-ligand 1 (PD-L1) expression in ≥ 25% of tumor cells and an ECOG PS2 treated with 1L durvalumab. This safety analysis was triggered by the SAKK data and safety monitoring board due to a high mortality rate observed after the recruitment of the first 21 patients. Methods: This single-arm phase II study recruited patients with metastatic NSCLC with PD-L1 in ≥ 25% and ECOG PS2. Patients received durvalumab 1500 mg every four weeks. The trial aims to recruit 48 patients in total. This report includes safety analyses only. Adverse events (AEs) were assessed using National Cancer Institute Common Terminology Criteria for AEs (NCI CTCAE) Version 5.0. Efficacy data including the primary endpoint overall survival at 6 months and secondary endpoints (objective response rate, progression-free survival, and quality of life) will be reported at a later time point. Results: The data from 21 patients were available at this interim safety analysis. Among these, 13 deaths (13/21; 62%) were reported, including one treatment-related fatal colonic perforation at 9 months after treatment initiation (1/13; 8%). Twelve deaths were not treatment-related (12/13; 92%), and mostly attributed to tumor progression (10/13; 77%). Of note, seven deaths (7/13; 54%) occurred during the first 5 weeks (range 0.6–4.7 weeks) after treatment initiation. Four (4/7; 57%) were respiratory failures attributed to tumor progression. One of these patients (25%) had pre-existing COPD, and three (75%) had baseline dyspnea grade 2–3 related to the tumor. Grade ≥ 3 treatment-related AEs (TRAEs) included colonic perforation (grade 5), abdominal pain, and colitis (grade 3 each) in one patient, and fatigue (grade 3) in another. Other Grade ≥ 3 AEs unrelated to treatment were all of pulmonary origin: lung infections (19%), dyspnea (24%), cough (5%), and bronchial obstruction (5%). Conclusions: 1L durvalumab in patients with ECOG PS2 and metastatic NSCLC with PD-L1 expression ≥ 25% resulted in an unexpectedly high number of fatal early events due to rapid tumor progression. We recommend to avoid treatment with 1 L durvalumab of patients who are highly symptomatic from the tumor, particularly those with respiratory symptoms. The study is continuing its accrual after an amendment excluding these patients. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the predominant cause of vision loss in the elderly with a major impact on ageing societies and healthcare systems. A major challenge in AMD management is the difficulty to determine the disease stage, the highly variable progression speed and the risk of conversion to advanced AMD, where irreversible functional loss occurs. In this study we developed an optical coherence tomography (OCT) imaging based spatio-temporal reference frame to characterize the morphologic progression of intermediate age-related macular degeneration (AMD) and to identify distinctive patterns of conversion to the advanced stages macular neovascularization (MNV) and macular atrophy (MA). We included 10,040 OCT volumes of 518 eyes with intermediate AMD acquired according to a standardized protocol in monthly intervals over two years. Two independent masked retina specialists determined the time of conversion to MNV or MA. All scans were aligned to a common reference frame by intra-patient and inter-patient registration. Automated segmentations of retinal layers and the choroid were computed and en-face maps were transformed into the common reference frame. Population maps were constructed in the subgroups converting to MNV (n=135), MA (n=50) and in non-progressors (n=333). Topographically resolved maps of changes were computed and tested for statistical significant differences. The development over time was analysed by a joint model accounting for longitudinal and right-censoring aspect. Significantly enhanced thinning of the outer nuclear layer (ONL) and retinal pigment epithelium (RPE)–photoreceptorinner segment/outer segment (PR-IS/OS) layers within the central 3 mm and a faster thinning speed preceding conversion was documented for MA progressors. Converters to MNV presented an accelerated thinning of the choroid and appearance changes in the choroid prior to MNV onset. The large-scale automated image analysis allowed us to distinctly assess the progression of morphologic changes in intermediate AMD based on conventional OCT imaging. Distinct topographic and temporal patterns allow to prospectively determine eyes with risk of progression and thereby greatly improving early detection, prevention and development of novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

After it was found that the gravity gradients observed by the Gravity field and steady-state Ocean Circulation Explorer (GOCE) satellite could be significantly improved by an advanced calibration, a reprocessing project for the entire mission data set was initiated by ESA and performed by the GOCE High-level processing facility (GOCE HPF). One part of the activity was delivering the gravity field solutions, where the improved level 1b and level 2 data serve as an input for global gravity field recovery. One well-established approach for the analysis of GOCE observations is the so-called time-wise approach. Basic characteristics of the GOCE time-wise solutions is that only GOCE observations are included to remain independent of any other gravity field observables and that emphasis is put on the stochastic modeling of the observations' uncertainties. As a consequence, the time-wise solutions provide a GOCE-only model and a realistic uncertainty description of the model in terms of the full covariance matrix of the model coefficients. Within this contribution, we review the GOCE time-wise approach and discuss the impact of the improved data and modeling applied in the computation of the new GO_CONS_EGM_TIM_RL06 solution. The model reflects the Earth's static gravity field as observed by the GOCE satellite during its operation. As nearly all global gravity field models, it is represented as a spherical harmonic expansion, with maximum degree 300. The characteristics of the model and the contributing data are presented, and the internal consistency is demonstrated. The updated solution nicely meets the official GOCE mission requirements with a global mean accuracy of about 2 cm in terms of geoid height and 0.6 mGal in terms of gravity anomalies at ESA's target spatial resolution of 100 km. Compared to its RL05 predecessor, three kinds of improvements are shown, i.e., (1) the mean global accuracy increases by 10–25%, (2) a more realistic uncertainty description and (3) a local reduction of systematic errors in the order of centimeters. [ABSTRACT FROM AUTHOR]

Letter to the Editor regarding "A comparative study of audiological outcomes and compliance between the Osia system and other bone conduction hearing implants" by Kim et al. In the paper by Gavilan et al. [[1]], the HearRing group divided implantable bone conduction hearing devices into Bone Anchored Implants (BAI) that are percutaneous and have a screw penetrating the skin, and Bone Conduction Implants (BCI) that are transcutaneous, where the entire implant is placed subcutaneously. In active BCI (Bonebridge, Osia), the implant itself is vibrating and thus directly driving the bone. [Extracted from the article]

Data sources The electronic databases Medline, the Cochrane Central Register of Controlled Trials, Embase, China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Data, ClinicalTrials.gov and WHO International Clinical Trials Registry Platform, from inception to September 2020, were searched to identify the eligible studies measuring the association between periodontal disease and Alzheimer's disease or mild cognitive impairment. Study selection Cohort, cross-sectional and case-control studies, without any language restrictions, were selected by two reviewers independently. Data extraction and synthesis Data extraction and quality assessment were performed by two reviewers independently. Data was synthesised quantitatively with meta-analyses using a random or fixed-effects model, with P <0.1 considered statistically significant. Quality assessment of cohort and case-control studies was carried out using the Newcastle-Ottawa scale (NOS) and quality assessment of cross-sectional studies was undertaken using the Agency for Healthcare Research and Quality (AHRQ) tool. Heterogeneity of included studies was assessed with I2. Results Thirteen studies, including five cross-sectional studies, five case-control studies, two retrospective cohort studies and one prospective cohort study were found to be eligible. Meta-analyses showed elevated risk for Alzheimer's disease (odds ratio = 1.78; random-effects model; significant heterogeneity) and mild cognitive impairment (odds ratio = 1.60; fixed-effects model; low heterogeneity) in patients with periodontal disease. One case-control study and all cohort studies had high quality, while four case-control studies had medium quality, as evaluated by the NOS. Among the cross-sectional studies evaluated by the AHRQ tool, only one had high quality, whereas other studies had medium quality. Conclusions Within the limitations of the included studies, the authors concluded that periodontal disease is related to an elevated risk of Alzheimer's disease and mild cognitive impairment. [ABSTRACT FROM AUTHOR]

The adsorption behavior of single CO molecules at 4 K bound to Au adatoms on a Ag(001) metal surface is studied with scanning tunneling microscopy (STM) and inelastic electron tunneling spectroscopy (IETS). In contrast to earlier observations two different binding configurations are observed—one on top of a Au adatom and the other one adsorbed laterally to Au on Ag(001). Moreover, IETS reveals different low-energy vibrational energies for the two binding sites as compared to the one for a single CO molecule bound to Ag(001). Density functional theory (DFT) calculations of the adsorption energies, the diffusion barriers, and the vibrational frequencies of the CO molecule on the different binding sites rationalize the experimental findings. [ABSTRACT FROM AUTHOR]

Pulmonary thromboembolism may be accompanied by pulmonary infarction. Even though pulmonary thromboembolism (PTE) is a frequently found cause of death at autopsy, pulmonary infarction accompanying PTE is a less common finding and may therefore easily be misinterpreted as infectious or cancerous lung disease. Appearance of pulmonary infarction in post-mortem imaging and acquisition parameters helping to identify pulmonary infarctions are not described yet. Based on a case of a 50-year-old man who died due to PTE and presented pulmonary infarction, we suggest using a pulmonary algorithm in post-mortem computed tomography combined with post-mortem magnetic resonance imaging of the lungs using conventional T1- and T2-weighted sequences. [ABSTRACT FROM AUTHOR]

Objectives: Early clinical trials showed promising outcomes with immune-checkpoint inhibitors (ICI) in a subset of patients with relapsed small-cell lung carcinoma (SCLC). The aim of this retrospective analysis was to assess the efficacy and safety of ICI for relapsed SCLC in a real-world patient population. Methods: Nine cancer centres in Switzerland contributed data to this cohort. Responses were assessed by the local investigators using standard RECIST v1.1 criteria. Progression-free survival (PFS) and overall survival (OS) were analysed by the Kaplan–Meier method. Associations between potential predictive markers and survival endpoints were probed by Cox proportional hazards. Results: Forty-five patients were included in the analysis. Median age was 63 years, 73% were males and 18% had an ECOG performance status (PS) ≥ 2. ICIs were given as second-line treatment in 60%. Twenty-four patients (53%) received ipilimumab with nivolumab. Twenty-eight patients (62%) had undergone irradiation (RT) prior to or during ICI. Overall response rate (ORR) was 29% and median PFS and OS were 2.3 and 6.5 months, respectively. Median duration of response was 9 months (95% CI 2.8–NA). Five patients maintained their response for > 6 months, all of them receiving combination treatment. There were no new safety signals. Conclusion: This is the first report of "real-world" data on ICI in relapsed SCLC also including patients with poor PS. Promising durable responses were observed. No biological prognostic marker could be identified. [ABSTRACT FROM AUTHOR]

Purpose: The enzyme O6-methylguanine-DNA methyltransferase (MGMT) is an important component of the DNA repair machinery. MGMT removes O6-methylguanine from the DNA by transferring the methyl group to a cysteine residue in its active site. Recently, we detected the single nucleotide polymorphism (SNP) rs12917 (C/T) in the MGMT sequence adjacent to the active site in Hodgkin lymphoma (HL) cell line KM-H2. We now investigated whether this SNP is also present in other HL cell lines and patient samples. Furthermore, we asked whether this SNP might have an impact on metabolic response in 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET), and on overall treatment outcome based on follow-up intervals of at least 34 months.Procedures: We determined the frequency of this MGMT polymorphism in 5 HL cell lines and in 29 pediatric HL (PHL) patients. The patient cohort included 17 female and 12 male patients aged between 4 and 18 years. After characterization of the sequence, we tested a possible association between rs12917 and age, gender, Ann Arbor stage, treatment group, metabolic response following two courses of OEPA (vincristine, etoposide, prednisone, and doxorubicin) chemotherapy, radiotherapy indication, and relapse status.Results: We detected the minor T allele in four of five HL cell lines. 11/29 patients carried the minor T allele whereas 18/29 patients showed homozygosity for the major C allele. Interestingly, we observed significantly better metabolic response in PHL patients carrying the rs12917 C allele resulting in a lower frequency of radiotherapy indication.Conclusion: MGMT polymorphism rs12917 seems to affect chemotherapy response in PHL. The prognostic value of this polymorphism should be investigated in a larger patient cohort. [ABSTRACT FROM AUTHOR]

Glycoside hydrolases, particularly cellulases, xylanases and mannanases, are essential for the depolymerisation of lignocellulosic substrates in various industrial bio-processes. In the present study, a novel glycoside hydrolase from Paenibacillus mucilaginosus (PmGH) was expressed in E. coli, purified and characterised. Functional analysis indicated that PmGH is a 130 kDa thermophilic multi-modular and multi-functional enzyme, comprising a GH5, a GH6 and two CBM3 domains and exhibiting cellulase, mannanase and xylanase activities. The enzyme displayed optimum hydrolytic activities at pH 6 and 60 °C and moderate thermostability. Homology modelling of the full-length protein highlighted the structural and functional novelty of native PmGH, with no close structural homologs identified. However, homology modelling of the individual GH5, GH6 and the two CBM3 domains yielded excellent models based on related structures from the Protein Data Bank. The catalytic GH5 and GH6 domains displayed a (β/α)8 and a distorted seven stranded (β/α) fold, respectively. The distinct homology at the domain level but low homology of the full-length protein suggests that this protein evolved by exogenous gene acquisition and recombination. [ABSTRACT FROM AUTHOR]

Background: The goal of this study was to evaluate if unenhanced PMCT HU values of liver pathologies differ from post-mortem HU values of non-pathologic liver tissue. Methods: Liver HU values were measured in five liver segments in PMCT unenhanced datasets of 214 forensic cases (124 male, 90 female, mean age 54.3 years). Liver HU values were compared with corresponding histologic liver findings. HU values of non-pathologic livers were compared to HU values of liver pathologies. Results: A total of 64 non-pathologic livers (mean HU 58.32, SD 8.91) were assessed. Histologic diagnosed liver pathologies were as follows: steatosis (n = 121 (grade I n = 61, grade II n = 37, grade III n = 23)), fibrosis (n = 10), and cirrhosis (n = 19). HU values of the livers exhibiting severe steatosis (mean HU 32.44, SD 13.76), fibrosis (mean HU 44.7, SD 16.31), and cirrhosis (mean HU 50.59, SD 9.42) significantly differed to HU values of non-pathologic livers at ANOVA testing. Conclusion: PMCT unenhanced liver HU value measurements may be used as an additional method to detect unspecific liver-pathology. Values below 30 HU may specifically indicate severe steatosis. [ABSTRACT FROM AUTHOR]

The effect of long-term environmental changes on sea bird populations with respect to changes in their breeding and foraging habitats is difficult to assess due to the scarcity of records that go beyond direct observational data. Information on the past distribution of snow petrel Pagodroma nivea (Forster) breeding colonies can be obtained from deposits of their proventricular stomach oil, so-called Antarctic mumiyo. In our study, we present 14C ages of mumiyo deposits from northern and southern Prince Charles Mountains, East Antarctica, to reconstruct the timing of snow petrel occupation at these inland breeding localities. 14C ages indicate a minimum age of snow petrel occupation of 3680 cal year bp. The colonisation post-dates the de-glacial local and regional ice sheet retreat by several thousand years. This either suggests limited accessibility of the inland sites or a lack of suitable nesting locations prior to the Mid-Holocene and/or changes in the marine habitat affecting access to the foraging grounds. 14C ages of mumiyo deposits from Vestfold and Larsemann Hills to the east of Prydz Bay point to a regional pattern of snow petrel dispersal starting in the Mid-Holocene. This suggests environmental changes in the foraging habitat to be the most likely drivers for extending breeding site locations of snow petrels to more inland ice-free areas in the Prydz Bay Region. [ABSTRACT FROM AUTHOR]

Background: Perisellar infiltration may be responsible for incomplete removal of pituitary tumors. Since intraoperative visualization of parasellar structures is difficult during transsphenoidal surgery, we are describing the use of intraoperative direct contact ultrasound (IOUS).Methods: Within 5 years, in 113 transsphenoidal operations (58 male, 55 female, age 14-81 years, 110 pituitary adenomas (mean diameter 26.6 mm, 69 non-secreting adenomas, 41 secreting adenomas), and 1 of each Rathke's cleft cyst, craniopharyngioma, and xanthogranuloma), IOUS was applied. After wide opening of the sellar floor and removal of the intrasellar tumor portions, a commercially available side fire ultrasound probe is introduced, and in direct contact to the sellar envelope, the perisellar space is scanned perpendicular to the axis of the working channel. We compared the results of IOUS to postoperative MRI after 3-6 months.Results: Identification of the intracavernous ICA, the anterior optic pathway, and the ACA, was possible, it was safe to operate close to them. In 65 operations (58%), further resection of tumor remnants was performed after IOUS. In this selected series, complete resection of tumors (stated by postoperative MRI after 3-6 months) was achieved in 75 operations (66%) and remission was achieved in 18 operations of secreting adenomas (44%). Compared to MRI after 3 to 6 months, the sensitivity of IOUS was 0.568 and the specificity was 0.907. No complications related to IOUS were seen.Conclusions: Visualization of the perisellar compartments by IOUS is easy and fast to perform. It allows the surgeon to identify resectable tumor remnants intraoperatively, which otherwise could be missed. [ABSTRACT FROM AUTHOR]

Background: In forensic autopsy, the analysis of stomach contents is important when investigating drowning cases. Three-layering of stomach contents may be interpreted as a diagnostic hint to drowning due to swallowing of larger amounts of water or other drowning media. The authors experienced frequent discrepancies of numbers of stomach content layering in drowning cases between post-mortem computed tomography (PMCT) and autopsy in forensic casework. Therefore, the goal of this study was to compare layering of stomach contents in drowning cases between PMCT and forensic autopsy.Methods: Drowning cases (n = 55; 40 male, 15 female, mean age 45.3 years; mean amount of stomach content 223 ml) that received PMCT prior to forensic autopsy were retrospectively analyzed by a forensic pathologist and a radiologist. Number of layers of stomach content in PMCT were compared to number of layers at forensic autopsy.Results: In 28 of the 55 evaluated drowning cases, a discrepancy between layering of stomach contents at autopsy compared to PMCT was observed: 1 layer at autopsy (n = 28): 50% discrepancy to PMCT, 2 layers (n = 20): 45% discrepancy, and 3 layers (n = 7): 71.4% discrepancy. Sensitivity of correctly determining layering (as observed at forensic autopsy) in PMCT was 52% (positive predictive value 44.8%). Specificity was 46.6% (negative predictive value 53.8%). In a control group (n = 35) of non-drowning cases, three-layering of stomach contents was not observed.Conclusion: Discrepancies of observed numbers of stomach content layers between PMCT and forensic autopsy are a frequent finding possibly due to stomach content sampling technique at autopsy and movement of the corpse prior to PMCT and autopsy. Three-layering in PMCT, if indeed present, may be interpreted as a hint to drowning. [ABSTRACT FROM AUTHOR]

This meta-analysis combines the results of nine ischemic stroke trials, assessing efficacy of Cerebrolysin on global neurological improvement during early post-stroke period. Cerebrolysin is a parenterally administered neuropeptide preparation approved for treatment of stroke. All included studies had a prospective, randomized, double-blind, placebo-controlled design. The patients were treated with 30-50 ml Cerebrolysin once daily for 10-21 days, with treatment initiation within 72 h after onset of ischemic stroke. For five studies, original analysis data were available for meta-analysis (individual patient data analysis); for four studies, aggregate data were used. The combination by meta-analytic procedures was pre-planned and the methods of synthesis were pre-defined under blinded conditions. Search deadline for the present meta-analysis was December 31, 2016. The nonparametric Mann-Whitney (MW) effect size for National Institutes of Health Stroke Scale (NIHSS) on day 30 (or 21), combining the results of nine randomized, controlled trials by means of the robust Wei-Lachin pooling procedure (maximin-efficient robust test), indicated superiority of Cerebrolysin as compared with placebo (MW 0.60, P < 0.0001, N = 1879). The combined number needed to treat for clinically relevant changes in early NIHSS was 7.7 (95% CI 5.2 to 15.0). The additional full-scale ordinal analysis of modified Rankin Scale at day 90 in moderate to severe patients resulted in MW 0.61 with statistical significance in favor of Cerebrolysin (95% CI 0.52 to 0.69, P = 0.0118, N = 314). Safety aspects were comparable to placebo. Our meta-analysis confirms previous evidence that Cerebrolysin has a beneficial effect on early global neurological deficits in patients with acute ischemic stroke. [ABSTRACT FROM AUTHOR]

The goal of the present study was to evaluate if quantitative postmortem cardiac 3-T magnetic resonance (QPMCMR) T1 and T2 relaxation times and proton density values of histopathological early acute and chronic myocardial infarction differ to the quantitative values of non-pathologic myocardium and other histopathological age stages of myocardial infarction with regard to varying corpse temperatures. In 60 forensic corpses (25 female, 35 male), a cardiac 3-T MR quantification sequence was performed prior to autopsy and cardiac dissection. Core body temperature was assessed during MR examinations. Focal myocardial signal alterations in synthetically generated MR images were measured for their T1, T2, and proton density (PD) values. Locations of signal alteration measurements in PMCMR were targeted at heart dissection, and myocardial tissue specimens were taken for histologic examinations. Quantified signal alterations in QPMCMR were correlated to their according histologic age stage of myocardial infarction, and quantitative values were corrected for a temperature of 37 °C. In QPMCMR, 49 myocardial signal alterations were detected in 43 of 60 investigated hearts. Signal alterations were diagnosed histologically as early acute (n = 16), acute (n = 10), acute with hemorrhagic component (n = 9), subacute (n = 3), and chronic (n = 11) myocardial infarction. Statistical analysis revealed that based on their temperature-corrected quantitative T1, T2, and PD values, a significant difference between early acute, acute, and chronic myocardial infarction can be determined. It can be concluded that quantitative 3-T postmortem cardiac MR based on temperature-corrected T1, T2, and PD values may be feasible for pre-autopsy diagnosis of histopathological early acute, acute, and chronic myocardial infarction, which needs to be confirmed histologically. [ABSTRACT FROM AUTHOR]

Monitoring of vinyl acetate–ethylene (VAE) processes plays a crucial role in achieving high process efficiency in industry while ensuring process safety and the needed product quality. Different methods are applied along the process chain, which includes production of the VAE polymer dispersion in high pressure reactors, degassing of the product back to atmospheric pressure, storage and shipping, and spray drying of the polymer to create a dispersible polymer powder. Properties of interest to monitor on a routine basis can be process related, such as heat output and conversion, or product related, such as total solids, viscosity, pH, particle size distribution, moisture content, and chemical composition. Other techniques can also be used to gain further knowledge of the process (e.g., mixing behavior) and of the product (e.g., polymer structure, volatile organic compounds, and biostability). Different monitoring techniques are discussed, focusing on their applicability in the industrial process under consideration. [ABSTRACT FROM AUTHOR]

This meta-analysis combines the results of two identical stroke studies (CARS-1 and CARS-2) assessing efficacy of Cerebrolysin on motor recovery during early rehabilitation. Cerebrolysin is a parenterally administered neuropeptide preparation approved for the treatment of stroke. Both studies had a prospective, randomized, double-blind, placebo-controlled design. Treatment with 30 ml Cerebrolysin once daily for 3 weeks was started 24-72 h after stroke onset. In addition, patients participated in a standardized rehabilitation program for 21 days that was initiated within 72 h after stroke onset. For both studies, the original analysis data were used for meta-analysis (individual patient data analysis). The combination of these two studies by meta-analytic procedures was pre-planned, and the methods were pre-defined under blinded conditions. The nonparametric Mann-Whitney (MW) effect size of the two studies on the ARAT score on day 90 indicated superiority of Cerebrolysin compared with placebo (MW 0.62, P < 0.0001, Wei-Lachin pooling procedure, day 90, last observation carried forward; N = 442). Also, analysis of early benefit at day 14 and day 21 by means of the National Institutes of Health Stroke Scale, which is regarded as most sensitive to early improvements, showed statistical significance (MW 0.59, P < 0.002). The corresponding number-needed-to-treat (NNT) for clinically relevant changes in early NIHSS was 7.1 (95% CI: 4 to 22). Cerebrolysin had a beneficial effect on motor function and neurological status in early rehabilitation patients after acute ischemic stroke. Safety aspects were comparable to placebo, showing a favourable benefit/risk ratio. [ABSTRACT FROM AUTHOR]

First, likelihood ratio statistics for checking the hypothesis of equal variances of two-dimensional Gaussian vectors are derived both under the standard $\left (\sigma ^{2}_{1},\sigma ^{2}_{2},\varrho \right)$ -parametrization and under the geometric ( a, b, α)-parametrization where a and b are the variances of the principle components and α is an angle of rotation. Then, the likelihood ratio statistics for checking the hypothesis of equal scaling parameters of principle components of p-power exponentially distributed two-dimensional vectors are considered both under independence and under rotational or correlation type dependence. Moreover, the role semi-inner products play when establishing various likelihood equations is demonstrated. Finally, the dependent p-generalized polar method and the dependent p-generalized rejection-acceptance method for simulating star-shaped distributed vectors are presented. [ABSTRACT FROM AUTHOR]

Copyright of Der Unfallchirurg is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

According to the concept of fetal programming, prenatal distress has long-lasting consequences on the offspring's health later in life. The hypothalamic-pituitary-adrenal axis is considered a mediating system by which maternal distress is transferred to the fetus in intrauterine environment. In this longitudinal explorative study on 30 mother-child-dyads, reported maternal distress and salivary cortisol were collected during pregnancy. Infant temperament, motor and cognitive development were assessed at 16 months. Additionally, infant cortisol levels throughout the day and in reaction to a psycho-social stressor where measured. As expected, infants whose mothers had experienced higher prenatal distress expressed a more difficult temperament and lower fine motor development at 16 months. No association could be shown between prenatal maternal distress and infant salivary cortisol. [ABSTRACT FROM AUTHOR]

Starting from a norm-contoured or star-shaped, bivariate vector distribution giving rise to a generalized (non-Euclidean) radius coordinate, the conditional density of the polar angle given the fixed radius variable is derived and visualized. A model is fitted to real life data. [ABSTRACT FROM AUTHOR]

Introduced in the late 90s, the active middle ear implant Vibrant Soundbridge (VSB) is nowadays used for hearing rehabilitation in patients with mild to severe sensorineural hearing loss (SNHL) unable to tolerate conventional hearing aids. In experienced hands, the surgical implantation is fast done, safe and highly standardized. Here, we present a systematic review, after more than 15 years of application, to determine the efficacy/effectiveness and cost-effectiveness, as well as patient satisfaction with the VSB active middle ear implant in the treatment of mild to severe SNHL. A systematic search of electronic databases, investigating the safety and effectiveness of the VSB in SNHL plus medical condition resulted in a total of 1640 papers. After removing duplicates, unrelated articles, screening against inclusion criteria and after in-depth screening, the number decreased to 37 articles. 13 articles were further excluded due to insufficient outcome data. 24 studies remained to be systematically reviewed. Data was searched on safety, efficacy and economical outcomes with the VSB. Safety-oriented outcomes included complication/adverse event rates, damage to the middle/inner ear, revision surgery/explant rate/device failure and mortality. Efficacy outcomes were divided into audiological outcomes, including hearing thresholds, functional gain, speech perception in quiet and noise, speech recognition thresholds, real ear insertion gain and subjective outcomes determined by questionnaires and patient-oriented scales. Data related to quality of life (QALY, ICER) were considered under economical outcomes. The VSB turns out to be a highly reliable and a safe device which significantly improves perception of speech in noisy situations with a high sound quality. In addition, the subjective benefit of the VSB was found to be mostly significant in all studies. Finally, implantation with the VSB proved to be a cost-effective and justified health care intervention. [ABSTRACT FROM AUTHOR]