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High medication prices can create a financial burden for patients and reduce medication initiation. To improve decision making, public policy is supporting development of tools to provide real-time prescription drug prices. We reviewed the literature on medication cost conversations to characterize the context in which these tools may be used. Our review included 42 articles: a median of 84% of patients across four clinical specialties reported a desire for cost conversations ( n = 7 articles) but only 23% reported having held a cost conversation across six specialties ( n = 16 articles). Non-White and older patients were less likely to report having held a cost conversation than White and younger patients in 9 of 13 and 5 of 9 articles, respectively, examining these associations. Our review indicates that tools providing price information may not result in improved decision making without complementary interventions that increase the frequency of cost conversations with a focus on protected groups.

Purpose Our study analyzes the influence of minimally invasive vs. open surgery on the postoperative need for nursing care in patients with colorectal carcinoma. Colorectal cancer is an age-related disease, and oncologic surgery is increasingly performed in elderly patients. Long-term effects of the procedural choice on patients’ self-sufficiency and autonomy have not been scientifically addressed so far. Methods Multivariable logistic regression models based on claims data from a statutory health insurer (AOK, Baden-Württemberg, Germany) were applied to assess potential risk factors for assignment patients to a nursing care level, a German scale to categorize individual need for nursing care, at 12 and 36 months after colorectal cancer surgery. Results A total of 3996 patients were eligible to be included in the analysis. At 36 months postoperatively, 44 of 427 (10.3%) patients after minimally invasive colon cancer surgery and 231 of 1287 (17.9%) patients after open procedure were newly graded into a nursing care level (OR = 0.62, 95%CI = 0.44–0.90, p = 0.010). Thirty-four of 251 (13.5%) patients receiving minimally invasive rectal cancer surgery compared to 142 of 602 (23.6%) patients after open approach were newly assigned to a nursing care level (OR = 0.53, 95%CI = 0.34–0.81, p = 0.003). Conclusions Laparoscopically assisted resection of colorectal cancer seems to be superior in preserving physical autonomy of elderly patients with colorectal cancer.

The treatment of advanced basal cell carcinoma (BCC) often requires therapies beyond local surgical excision or radiation due to the invasiveness of the tumor. Historically, cytotoxic chemotherapy was used to treat advanced BCC, but with limited data, no standard regimens were established. The discovery of cyclopamine, a natural inhibitor in the Hedgehog pathway, led to the development of the 2 currently approved Hedgehog inhibitors, vismodegib and sonidegib. Both agents are indicated for locally advanced BCC, while vismodegib is also indicated for metastatic BCC. In patients who progress on hedgehog inhibitors or cannot tolerate hedgehog inhibitors, the programmed cell death protein 1 inhibitor cemiplimab can be used to treat locally advanced or metastatic disease. Complex cases of locally advanced or metastatic BCC may be best discussed through a multidisciplinary approach in order to determine the optimal treatment approach for the individual patient.

Introduction Electronic patient-reported outcomes (ePRO) are increasingly recognized in health care, as they have been demonstrated to improve patient outcomes in cancer, but have been less studied in rare hematological diseases. The aim of this study was to develop and test the feasibility of an ePRO system specifically customized for aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH). Methods After performing a user-centered design evaluation an ePRO system for AA and PNH patients could be customized and the application was tested by patients and their medical teams for 6 months. Symptom-reporting triggered self-management advice for patients and prompts them to contact clinicians in case of severe symptoms, while the medical team received alerts of severe symptoms for patient care. Results All nine included patients showed a high adherence rate to the weekly symptom-reporting (72%) and reported high satisfaction. The system was rated high for usage, comprehensibility, and integration into daily life. Most patients (78%) would continue and all would recommend the application to other AA/PNH patients. Technical performance was rarely a barrier and healthcare providers saw ePRO-AA-PNH as a useful supplement, but the lacking integration into the hospital information system was identified as a major barrier to usage. Conclusion An ePRO system customized for AA and PNH was feasible in terms of adherence, satisfaction, and performance, showing a high potential for these rare conditions in terms of data collection and patient guidance. However, the integration into clinical workflows is crucial for further routine use. Trial registration ClinicalTrials.gov NCT04128943.

A pericellular basket is a presynaptic configuration of numerous axonal boutons outlining a target neuron soma and its proximal dendrites. Recent studies show neurochemical diversity of pericellular baskets and suggest that neurotransmitter usage together with the dense, soma-proximal boutons may permit strong input effects on different time scales. Here we review the development, distribution, neurochemical phenotypes, and possible functions of pericellular baskets. As an example, we highlight pericellular baskets formed by projections of certain Pet1/Fev neurons of the serotonergic raphe nuclei. We propose that pericellular baskets represent convergence sites of competition or facilitation between neurotransmitter systems on downstream circuitry, especially in limbic brain regions, where pericellular baskets are widespread. Study of these baskets may enhance our understanding of monoamine regulation of memory, social behavior, and brain oscillations.

Introduction Vertebral fractures in patients with bone density reduction are often a major challenge for the surgeon, as reduced bone density can lead to screw loosening. Several options are available to determine bone density preoperatively. In our study, we investigated the correlation of Hounsfield units (HU) of a contrast medium computed tomography (CT) to the bone density values of a quantitative computed tomography (QCT) and computed a formula to estimate bone density values using HU. Materials and methods In our retrospective data analysis, we examine 98 vertebral bodies from 35 patients who received a contrast medium CT of the spine and a QCT, performed no longer than 1 month apart. The determined HU from the contrast medium CT were compared with the bone density values of the QCT and examined for correlations. Linear logistic regression was used to estimate bone density values base on HU. Results A strong correlation was found between the HU measured in the CT and the bone density values (r = 0.894, p Conclusions Bone density values correlate well to HU measured in contrast medium CT. Using simple formula, the bone density of a contrast medium CT of vertebral bodies can be estimated based on HU without additional examinations and unnecessary costs.

High-throughput sequencing describes multiple alterations in individual tumors, but their functional relevance is often unclear. Clinic-close, individualized molecular model systems are required for functional validation and to identify therapeutic targets of high significance for each patient. Here, we establish a Cre-ERT2-loxP (causes recombination, estrogen receptor mutant T2, locus of X-over P1) based inducible RNAi- (ribonucleic acid interference) mediated gene silencing system in patient-derived xenograft (PDX) models of acute leukemias in vivo. Mimicking anti-cancer therapy in patients, gene inhibition is initiated in mice harboring orthotopic tumors. In fluorochrome guided, competitive in vivo trials, silencing of the apoptosis regulator MCL1 (myeloid cell leukemia sequence 1) correlates to pharmacological MCL1 inhibition in patients´ tumors, demonstrating the ability of the method to detect therapeutic vulnerabilities. The technique identifies a major tumor-maintaining potency of the MLL-AF4 (mixed lineage leukemia, ALL1-fused gene from chromosome 4) fusion, restricted to samples carrying the translocation. DUX4 (double homeobox 4) plays an essential role in patients’ leukemias carrying the recently described DUX4-IGH (immunoglobulin heavy chain) translocation, while the downstream mediator DDIT4L (DNA-damage-inducible transcript 4 like) is identified as therapeutic vulnerability. By individualizing functional genomics in established tumors in vivo, our technique decisively complements the value chain of precision oncology. Being broadly applicable to tumors of all kinds, it will considerably reinforce personalizing anti-cancer treatment in the future., Preclinical molecular models are useful that mimic a patient´s response to targeted therapy. Here, the authors establish an in vivo inducible RNAi-mediated gene silencing system in patient-derived xenograft models of acute leukemia to identify individual vulnerabilities and therapeutic targets.

Background The project "Ulcus Cruris Care" aims to improve primary care for patients with venous leg ulcer (VLU) in General Practitioner (GP) practices using a complex intervention comprised of educational components, standardized treatment recommendations, computer-assisted documentation, and case management by non-physician medical assistants (MAs). Prior to implementing and testing the intervention components in general practices, in-depth exploration of current outpatient treatment of VLU patients and relevant implementation determinants was pursued. Methods A mixed-methods study explored views of GPs, MAs, and patients regarding current VLU outpatient care and the planned intervention components to identify potential implementation determinants. Data were collected through semi-structured guide-based telephone interviews (n = 29) and a survey questionnaire (n = 28). Interviews were transcribed verbatim. Analysis was inductive initially and finalized in a deductive-inductive approach based on domains of the Theoretical Domains Framework to support structuring of relevant implementation determinants. Survey data were analyzed descriptively. Results Current VLU outpatient care was described as frequently tailored to individual wounds and gradient. In general, workload was shared by GPs (diagnostics, counselling) and MAs (wound care). All care providers were aware of compression therapy, yet not all of them considered it essential for VLU care. Standardized operating procedures and educational components including e-learning were considered supportive. Stronger involvement of non-physician assistants was seen as opportunity to optimize VLU care. Concerns were identified regarding integration of software-supported case management into daily practice routines and regarding potential limitations in decision-making autonomy when using standard operating procedures. Conclusions Findings in this study emphasize a need for educational interventions addressing VLU care providers as well as patients, particularly with regards to compression therapy. The conception of the planned intervention appears to be adequate and a structured guideline-based case management might be a promising approach for optimization of VLU treatment.

Background The surgical treatment of giant olfactory groove meningiomas (OGMs) with marked perilesional brain oedema is still a surgical challenge. After tumour resection, increase of brain oedema may occur causing dramatic neurological deterioration and even death of the patient. The objective of this paper is to describe surgical features of a two-step staged resection of these tumours performed to counter increase of postoperative brain oedema. Methods This two-step staged resection procedure was carried out in a consecutive series of 19 patients harbouring giant OGMs. As first step, a bifrontal craniectomy was performed followed by a right-sided interhemispherical approach. About 80% of the tumour mass was resected leaving behind a shell-shaped tumour remnant. In the second step, carried out after the patients’ recovery from the first surgery and decline of oedema, the remaining part of the tumour was removed completely followed by duro- and cranioplasty. Results Ten patients recovered quickly from first surgery and the second operation was performed after a mean of 12.4 days. In eight patients, the second operation was carried out later between day 25 and 68 due to surgery-related complications, development of a trigeminal zoster, or to a persisting frontal brain oedema. Mean follow-up was 49.3 months and all but one patient had a good outcome regardless of surgery-related complications. Conclusions Our results suggest that a two-step staged resection of giant OGMs minimizes the increase of postoperative brain oedema as far as possible and translates into lower morbidity and mortality.

Emotion values vary within and between individualistic and collectivistic cultural contexts. The form of collectivism prevalent in Latin America emphasizes simpatia, a cultural model that stresses the relational benefits of positivity but also the costs of negativity. This model was predicted to engender a pattern of emotion values distinct from that of the more commonly studied collectivist group, people of Asian heritage (PAH), among whom an emphasis on moderating positive and negative emotions is typically observed, and from people of European heritage (PEH), among whom authenticity in emotions is typically valued. College students of Latino (n = 659), Asian (n = 446), and European (n = 456) heritage living in the United States completed a study examining positive and negative emotion values. Mixed-model analysis of variance that included interactions among culture, emotion valence (positive, negative), value type (desirability, appropriateness), and response type (experience, expression) suggested distinct patterns of emotion values across groups. People of Latino heritage (PLH) rated positive emotions as more desirable and appropriate to experience and express than PAH (ps .05) compared with PAH and as similarly undesirable (ps > .05) but more inappropriate to experience (p < .001) compared with PEH. The emotion-value pattern that emerged was largely consistent with simpatia for PLH and provides new evidence of similarity and variation in emotion values in three distinct contexts. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

To test whether 2 conceptually overlapping constructs, dispositional optimism (generalized positive expectations) and optimistic bias (inaccurately low risk perceptions), may have different implications for smoking treatment engagement.Predominantly Black, low-income Southern Community Cohort study smokers (n = 880) self-reported dispositional optimism and pessimism (Life Orientation Test-Revised subscales: 0 = neutral, 12 = high optimism/pessimism), comparative lung cancer risk (Low/Average/High), and information to calculate objective lung cancer risk (Low/Med/High). Perceived risk was categorized as accurate (perceived = objective), optimistically-biased (perceivedobjective), or pessimistically-biased (perceivedobjective). One-way ANOVAs tested associations between dispositional optimism/pessimism and perceived risk accuracy. Multivariable logistic regressions tested independent associations of optimism/pessimism and perceived risk accuracy with cessation motivation (Low/High), confidence (Low/High), and precision treatment attitudes (Favorable/Unfavorable), controlling for sociodemographics and nicotine dependence.Mean dispositional optimism/pessimism scores were 8.41 (Dispositional optimism and lung cancer risk perception accuracy were unrelated. Dispositional optimism was associated with favorable engagement-related outcomes and optimistically-biased risk perception with unfavorable outcomes, reinforcing the distinctiveness of these constructs and their implications for smoking treatment. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

ObjectivesWe aimed to assess general practice (GP) trainees’ self-perception of surgical competencies and to explore longitudinal effects of a compact intervention.DesignWe performed a mixed-methods study including a before and after comparison in the intervention group (IG), a comparison of attendees and non-attendees (control group (CG)) and a qualitative evaluation of the intervention. Competencies were self-assessed through surveys. Semi-structured interviews were performed after 9 months.SettingIn 2019, a 2-day voluntary seminar focussing on minor surgery/injuries was offered on 13 occasions by educators from KWBW Verbundweiterbildungplus (Competence Centre for Postgraduate Medical Education Baden-Württemberg).ParticipantsAll enrolled GP trainees were offered participation. GP trainees who did not attend a seminar (non-attendees) were recruited for CG after the 13th intervention.InterventionAttendees took part in an interactive, GP-oriented short course incorporating 270 min of focused minor surgery/injuries training (compact intervention) on the second day of the 2-day seminar.Results326 GP trainees (IG: n=257; CG: n=69) participated in the study. 17 attendees were interviewed. CG had more often experienced a surgical rotation (p=0.03) and reported higher interest in performing minor surgery in future practice (p=0.03). GP trainees self-rated their all-round competency in minor surgery as average (IG: 3.0±1.0, CG: 3.2±0.9, IG:CG p=0.06). After the intervention, attendees felt that surgical skills should be a core component of GP vocational training (p=0.05). After 9 months, attendees remembered a variety of content and valued the interactive, case-oriented, peer-to-peer approach in a mixed learning group. Some attendees reported they had started to overcome competency gaps in minor surgery.ConclusionsA compact intervention in minor surgery provides an ‘intense’ stimulus which could foster positive attitudes towards minor surgery and promote longitudinal personal development of related competencies in GP trainees, including those with little interest in surgery. Such measures appear crucial to support individual progress of GP trainees to provide comprehensive primary care.

The level of structural integration (LSI), a psychodynamic/psychoanalytic concept originally developed by the Operationalized Psychodynamic Diagnosis (OPD), provides a promising empirical approach that is recognized beyond the boundaries of psychoanalysis and is highly relevant for therapy and research. The aim of our study was to investigate the intersession experiences of patients in psychotherapy with different levels of structural integration. The sample consisted of 69 inpatients who were undergoing psychotherapeutic treatment. The patients were asked to complete the German version of the Intersession Experience Questionnaire (IEQ), the short version of the OPD Structure Questionnaire (OPD-SQS) and the Brief-Symptom Inventory (BSI). LSI is associated with the situations, contents and negative emotions in the intersession experiences of patients, as well as their symptom distress over the course of therapy. Furthermore, the level of structural integration is a significant predictor of outcomes. Patients with different LSI had different intersession experiences.

BackgroundA systems-level approach to smoking cessation treatment may optimize healthcare provider adherence to guidelines. Institutions such as the Veterans Health Administration (VHA) are unique in their systematic approach, but comparisons of provider behavior in different healthcare systems are limited.MethodsWe surveyed general medicine providers and specialists in a large academic health center (AHC) and its affiliated VHA in the Mid-South in 2017 to determine the cross-sectional association of healthcare system in which the provider practiced (exposure: AHC versus VHA) with self-reported provision of evidence-based smoking cessation treatment (delivery of counseling plus smoking cessation medication or referral) at least once in the past 12 months (composite outcome). Multivariable logistic regression with adjustment for specialty was performed in 2017–2019.ResultsOf 625 healthcare providers surveyed, 407 (65%) responded, and 366 (59%) were analyzed. Most respondents practiced at the AHC (273[75%] vs VHA 93[25%]) and were general internists (215[59%]); pulmonologists (39[11%]); hematologists/oncologists (69[19%]); and gynecologists (43[12%]). Most respondents (328[90%]) reported the primary outcome. The adjusted odds of evidence-based smoking cessation treatment were higher among VHA vs. AHC healthcare providers (aOR = 4.3; 95% CI 1.3–14.4;p = .02). Health systems differed by provision of individual treatment components, including smoking cessation medication use (98% VHA vs. 90% AHC,p = 0.02) and referral to smoking cessation services (91% VHA vs. 65% AHCp = 0.001).ConclusionsVHA healthcare providers were significantly more likely to provide evidence-based smoking cessation treatment compared to AHC healthcare providers. Healthcare systems’ prioritization of and investment in smoking cessation treatment is critical to improving providers’ adherence to guidelines.

Contains fulltext : 238670.pdf (Publisher’s version ) (Open Access) BACKGROUND: Growing prevalence of chronic diseases is a rising challenge for healthcare systems. The Primary Care Practice-Based Care Management (PraCMan) programme is a comprehensive disease management intervention in primary care in Germany aiming to improve medical care and to reduce potentially avoidable hospitalisations for chronically ill patients. OBJECTIVES: This study aimed to assess the effect of PraCMan on hospitalisation rate and related costs. METHODS: A retrospective propensity-score matched cohort study was performed. Reimbursement data related to patients treated in general practices between 1st July 2013 and 31st December 2017 were supplied by a statutory health insurance company (AOK Baden-Wuerttemberg, Germany) to compare hospitalisation rate and direct healthcare costs between patients participating in the PraCMan intervention and propensity-score matched controls following usual care. Outcomes were determined for the one-year-periods before and 12 months after beginning of participation in the intervention. RESULTS: In total, 6148 patients participated in the PraCMan intervention during the observation period and were compared to a propensity-score matched control group of 6148 patients from a pool of 63,446 eligible patients. In the one-year period after the intervention, the per-patient hospitalisation rate was 8.3% lower in the intervention group compared to control (p = 0.0004). Per-patient hospitalisation costs were 9.4% lower in favour of the intervention group (p = 0.0002). CONCLUSION: This study showed that the PraCMan intervention may be associated with a lower rate of hospital admissions and hospitalisation costs than usual care. Further studies may assess long-term effects of PraCMan and its efficacy in preventing known complications of chronic diseases.

Background Right ventricular outflow tract (RVOT) stenosis after repair of tetralogy of Fallot has been linked with favorable right ventricular remodeling but adverse outcomes. The aim of our study was to assess the hemodynamic impact and prognostic relevance of right ventricular pressure load in this population. Methods and Results A total of 296 patients with repaired tetralogy of Fallot (mean age, 17.8±7.9 years) were included in a prospective cardiovascular magnetic resonance multicenter study. Myocardial strain was quantified by feature tracking technique at study entry. Follow‐up, including the need for pulmonary valve replacement, was assessed. The combined end point consisted of ventricular tachycardia and cardiac death. A higher echocardiographic RVOT peak gradient was significantly associated with smaller right ventricular volumes and less pulmonary regurgitation, but lower biventricular longitudinal strain. During a follow‐up of 10.1 (0.1–12.9) years, the primary end point was reached in 19 of 296 patients (cardiac death, n=6; sustained ventricular tachycardia, n=2; and nonsustained ventricular tachycardia, n=11). A higher RVOT gradient was associated with the combined outcome (hazard ratio [HR], 1.03; 95% CI, 1.00–1.06; P =0.026), and a cutoff gradient of ≥25 mm Hg was predictive for cardiovascular events (HR, 3.69; 95% CI, 1.47–9.27; P =0.005). In patients with pulmonary regurgitation ≥25%, a mild residual RVOT gradient (15–30 mm Hg) was not associated with a lower risk for pulmonary valve replacement. Conclusions Higher RVOT gradients were associated with less pulmonary regurgitation and smaller right ventricular dimensions but were related to reduced biventricular strain and emerged as univariate predictors of adverse events. Mild residual pressure gradients did not protect from pulmonary valve replacement. These results may have implications for the indication for RVOT reintervention in this population.

Patients suffering from colorectal deep endometriosis (DE) experience gastrointestinal symptoms with almost the same frequency as gynecological pain symptoms. Preoperatively existing gastrointestinal symptoms may translate into pathological gastrointestinal quality of life index (GIQLI) and low anterior resection syndrome scores (LARS). This prospective questionnaire-based case control study aims to assess the prevalence of gastrointestinal complaints reflected by changes in LARS and GIQLI scores in patients with colorectal deep endometriosis prior to surgical treatment and compare those to a healthy control group.The study was conducted at the Hospital St. John of God in Vienna and included a total of 97 patients with histologically confirmed colorectal DE with radical surgical treatment and 96 women in whom DE was excluded via transvaginal sonography (TVS) or visually. Gastrointestinal symptoms reflected by LARS and GIQLI scores were evaluated presurgically and in controls.A total of 193 premenopausal patients were included in this study. A mean GIQLI of 90.7 ± 22.0 and 129.4 ± 11.1 was observed among patients and controls, respectively, showing a significantly higher morbidity concerning gastrointestinal symptoms and decreased quality of life (QoL) compared to healthy controls (p 0.001). The LARS score results demonstrated that 18.6% of the patients with bowel DE presented with a major LARS and 27.8% with a minor LARS presurgically compared to 2.1% and 9.4% of control patients, respectively (p 0.001).Patients with colorectal DE experience a quality of gastrointestinal symptoms translating into a decreased QoL and pathological GIQLI and LARS scores already presurgically. As a consequence, these instruments should be interpreted with caution.

Aims Changes in metabolism are known to contribute to tumour phenotypes. If and how metabolic alterations in brain tumours contribute to patient outcome is still poorly understood. Epigenetics impact metabolism and mitochondrial function. The aim of this study is a characterisation of metabolic features in molecular subgroups of isocitrate dehydrogenase mutant (IDHmut) and isocitrate dehydrogenase wildtype (IDHwt) gliomas. Methods We employed DNA methylation pattern analyses with a special focus on metabolic genes, large-scale metabolism panel immunohistochemistry (IHC), qPCR-based determination of mitochondrial DNA copy number and immune cell content using IHC and deconvolution of DNA methylation data. We analysed molecularly characterised gliomas (n = 57) for in depth DNA methylation, a cohort of primary and recurrent gliomas (n = 22) for mitochondrial copy number and validated these results in a large glioma cohort (n = 293). Finally, we investigated the potential of metabolic markers in Bevacizumab (Bev)-treated gliomas (n = 29). Results DNA methylation patterns of metabolic genes successfully distinguished the molecular subtypes of IDHmut and IDHwt gliomas. Promoter methylation of lactate dehydrogenase A negatively correlated with protein expression and was associated with IDHmut gliomas. Mitochondrial DNA copy number was increased in IDHmut tumours and did not change in recurrent tumours. Hierarchical clustering based on metabolism panel IHC revealed distinct subclasses of IDHmut and IDHwt gliomas with an impact on patient outcome. Further quantification of these markers allowed for the prediction of survival under anti-angiogenic therapy. Conclusion A mitochondrial signature was associated with increased survival in all analyses, which could indicate tumour subgroups with specific metabolic vulnerabilities.

Due to anticipated postoperative neuropsychological sequelae, patients with gliomas infiltrating the corpus callosum rarely undergo tumor resection and mostly present in a poor neurological state. We aimed at investigating the benefit of glioma resection in the corpus callosum, hypothesizing neuropsychological deficits were mainly caused by tumor presence. Between 01/2017 and 1/2020, 21 patients who underwent glioma resection in the corpus callosum were prospectively enrolled into this study. Neuropsychological function was assessed preoperatively, before discharge and after 6 months. Gross total tumor resection was possible in 15 patients, and in 6 patients subtotal tumor resection with a tumor reduction of 97.7% could be achieved. During a median observation time of 12.6 months 9 patients died from glioblastoma after a median of 17 months. Preoperatively, all cognitive domains were affected in up to two thirds of patients, who presented a median KPS of 100% (range 60–100%). After surgery, the proportion of impaired patients increased in all neurocognitive domains. Most interestingly, after 6 months, significantly fewer patients showed impairments in attention, executive functioning, memory and depression, which are domains considered crucial for everyday functionality. Thus, the results of our study strongly support our hypothesis that in patients with gliomas infiltrating the corpus callosum the benefit of tumor resection might outweigh morbidity.

Background The introduction of new therapy modalities has significantly improved the outcome of aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH) patients. However, relatively little is known about the exact disease burden of AA/PNH since standardized assessments of symptoms including health-related quality of life (HRQoL) are frequently missing or inadequately designed for this rare patient group. We aimed to develop AA/PNH-specific questionnaires for self-reporting of symptoms, which could be included in electronic platforms for data collection and patient care. Methods By scoping review, we extracted any reported symptoms in AA/PNH and their prevalence from the literature (Phase I). Consensus rounds with patients and medical experts were conducted to identify core symptoms reported in the literature and to add missing items (Phase II). Ultimately, AA/PNH-specific patient-reported outcome (PRO) questionnaires including the selected measures were designed (Phase III). Results AA symptoms from 62 and PNH symptoms from 45 observational studies were extracted from the literature. Twenty-four patients and seven medical experts identified 11 core symptoms including HRQoL issues after three consensus rounds. Significant differences in the symptom ranking of patients versus medical experts could be observed. Therefore, patient- as well as expert-centered PRO questionnaires in AA and PNH were created following the concepts of validated instruments. Conclusion The development of symptom self-reporting questionnaires for AA and PNH was feasible and the disease-specific PRO questionnaires can now be validated within a web-based workflow in a subsequent feasibility study.

Background With refinements in diagnosis and therapy of gliomas, the importance of survival time as the sole outcome parameter has decreased, and patient-centered outcome parameters have gained interest. Pursuing a profession is an indispensable component of human happiness. The aim of this study was to analyze the professional outcomes besides their neuro-oncological and functional evaluation after surgery for gliomas in eloquent areas. Methods We assessed neuro-oncological and functional outcomes of patients with gliomas WHO grades II and III undergoing surgery between 2012 and 2018. All patients underwent routine follow-up and adjuvant treatment. Treatment and survival parameters were collected prospectively. Repercussions of the disease on the patients’ professional status, socio-economic situation, and neurocognitive function were evaluated retrospectively with questionnaires. Results We analyzed data of 58 patients with gliomas (WHO II: 9; III: 49). Median patient age was 35.8 years (range 21–63 years). Awake surgery techniques were applied in 32 patients (55.2%). Gross total and subtotal tumor resections were achieved in 33 (56.9%) and 17 (29.3%) patients, respectively, whereas in 8 patients (13.8%) resection had to remain partial. Most patients (n = 46; 79.3%) received adjuvant treatment. Median follow up was 43.8 months (range 11–82 months). After treatment 41 patients (70.7%) were able to resume a working life. Median time until returning to work was 8.0 months (range 0.2–22.0 months). To be younger than 40 at the time of the surgery was associated with a higher probability to return to work (p Conclusion The ability to resume professional activities following brain tumor surgery is an important patient-oriented outcome parameter. We found that the majority of patients with gliomas were able to return to work following surgical and adjuvant treatment. Preservation of neurological function is of utmost relevance for individual patients´ quality of life.

Background The role of reactive thrombocytosis in non-aneurysmal subarachnoid hemorrhage (NA-SAH) is largely unexplored to date. Therefore, the impact of a quantitative thrombocyte dynamic in patients with NA-SAH and its clinical relevance were analyzed in the present study. Methods In this retrospective analysis, 113 patients with nontraumatic and NA-SAH treated between 2003 and 2015 at our institution were included. World Federation of Neurosurgical Societies admission status, cerebral vasospasm, delayed infarction, hydrocephalus, need for ventriculoperitoneal (VP) shunt, and Fisher grade were analyzed for their association with reactive thrombocytosis. Results Reactive thrombocytosis was not associated with hydrocephalus (p ≥ 0.05), need for VP shunt implantation (p ≥ 0.05), cerebral vasospasm (p ≥ 0.05), or delayed cerebral ischemia (p ≥ 0.05). Conclusion Our study is the first to investigate the role of thrombocyte dynamics, reactive thrombocytosis, and the clinical course of NA-SAH patients. Our analysis showed no significant impact of thrombocyte count on NA-SAH sequelae.

Pulmonary embolism (PE) due to deep vein thrombosis is a complication with severe morbidity and mortality rates. Neurocritical care patients constitute an inhomogeneous cohort with often strict contraindications to conventional embolism treatment. The aim of the present study is to identify risk factors for pulmonary embolism for intensified risk stratification in this demanding cohort. In this retrospective analysis, 387 neurocritical care patients received computed tomography for clinical suspicion of PE (304 neurosurgical and 83 neurological patients). Analysed parameters included age, gender, disease pattern, the presence of deep vein thrombosis, resuscitation, in-hospital mortality, present anticoagulation, coronary artery disease, diabetes mellitus, smoking status, hypertension and ABO blood type. Computed tomography confirmed 165 cases of pulmonary embolism among 387 patients with clinical suspicion of pulmonary embolism (42%). Younger age (p p p p p

Gratitude is positively associated with health and well-being. Past studies of gratitude have primarily focused on the distinct cultural context of European Americans. The current studies aimed to extend gratitude research to Latino and East Asian Americans, 2 collectivistic contexts known to differently value positive emotions. Two studies explored whether Latino and East Asian Americans varied in gratitude experience and whether the disposition toward gratitude was associated with well-being for both. In Study 1, participants completed measures of the emotional experience and expression of gratitude. Latino Americans rated the desirability, appropriateness, frequency, and intensity of their gratitude experience-expression higher than did East Asian Americans. Moreover, European Americans' gratitude experience and expression was similar to those of Latino Americans and higher than those of East Asian Americans. In Study 2, participants completed measures of gratitude disposition and indicators of well-being. Latino Americans reported a higher disposition toward gratitude than did East Asian Americans. Higher disposition toward gratitude was associated with higher self-esteem and with less loneliness and perceived stress across groups. However, the strength of the association of gratitude with subjective health and depressive symptoms varied by group in theoretically expected ways. The promising possibilities of extending research on gratitude to culturally diverse groups is discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Intracranial haemorrhage (ICH) is associated with permanent neurological disability resulting in deterioration of the quality of life (QoL). Our study assesses QoL in patients with ruptured arteriovenous malformation (AVM) in long-term follow-up at least five years after ICH and compares their QoL with the QoL of patient with non-ruptured AVM.Using the Quality of Life Scale (QOLS), the Patient Health Questionnaire (PHQ-9) for depressive symptoms, and the socioeconomic status (SES), a prospective assessment was performed. The modified Rankin Scale (mRS) was assessed for outcome.Of 73 patients, 42 (57.5%) had ruptured (group 1) and 31 (42.5%) a non-ruptured AVM (group 2). Mean follow-up time was 8.6 ± 3.9 years (8.5 ± 4.2 years in group 1 and 8.9 ± 3.7 years in group 2). Favourable outcome (mRS 0-1) was assessed in 60 (83.3%) and unfavourable in 12 (16.7%) patients. Thirty-one of 42 patients (73.8%) in group 1 and 29 of 30 patients in group 2 (96.7%) had favourable outcomes. Mean QOLS was 85.6 ± 14.1 (group 1 86.1 ± 15.9, group 2 84.9 ± 11.4). Patients in group 1 did not show a significant difference in QoL compared to patients in group 2 (p = 0.23). Additional analyses in group 2 (rho = - 0.73; p 0.01) and in untreated AVM patients (rho = - 0.81; p 0.01) showed a strong correlation between QOLS and PHQ-9.Long-term follow-up showed no difference in the QoL between patients with and without ICH caused by brain AVM. Outcome- and QoL-scores were high in both groups. Further studies are necessary to evaluate depression and anxiety symptoms in patients with AVM.

Background Venous leg ulcers (VLU) have a prevalence of 1–2% in developed countries, and affected patients are severely and long-term impaired in daily activities, work, and social participation. Evidence-based outpatient treatment based on compression therapy is frequently not implemented. The “Ulcus Cruris Care” project was established to develop a disease management concept to improve outpatient treatment for patients with VLU in German primary care. For this purpose, a multifaceted intervention was conceived consisting of an online training for general practitioners and medical assistants, standardized treatment recommendations, e-learning and print-based information for patients, and a software support for case management. The main aims of the Ulcus Cruris Care intervention are to promote standardized treatment according to current scientific knowledge, to facilitate case management for VLU patients exerted by medical assistants, and to support patient education and participation in the treatment process. The UCC trial was designed to evaluate the effectiveness of the Ulcus Cruris Care intervention. Methods The UCC trial is a prospective cluster-randomized controlled multicenter trial. Fifty GP practices are intended to be recruited and randomized 1:1 to intervention or control arm. Patients with venous leg ulcers will be recruited by participating GP practices, to include a total of 63 patients in each arm. The primary outcome is time to ulcer healing. Secondary outcomes comprise number and sizes of ulcers, recurrence, pain intensity according to the visual analog scale, health-related quality of life according to EQ-5D-5L, depressiveness according to Patient Health Questionnaire (PHQ-9), patient satisfaction according to the Patient Assessment of Chronic Illness Care (PACIC-5A) query, and adherence to VLU treatment. The outcome analysis of the UCC trial is accompanied by a health economic analysis and a process evaluation. Discussion The UCC trial will evaluate whether the Ulcus Cruris Care intervention may lead to faster wound healing, higher health-related quality of life, and lower use of medical resources. If the intervention turns out to have a positive impact on assessed outcomes, comprehensive implementation in primary care may be considered. Trial registration The trial protocol (version 1 as of July 19, 2021) has been registered in the German Clinical Trials Register on August 30, 2021 (DRKS00026126).

International literature reports an increase of the incidence of psychological disorders because of the COVID-19 pandemic. Especially young people and people with pre-existing psychological disorders are troubled by the pandemic. Objective of this study is the extent of psychological symptoms, the functioning and the treatment success of rehabilitation inpatients who participated in a medical and psychiatric rehabilitation in the year before the COVID-19 pandemic and those who participated during the COVID-19 phase.The data of N=1,715 rehabilitation inpatients who completed the rehabilitation before the lockdown in 2019 and N=707 rehabilitation inpatients who began in 2020 after the lockdown of the clinic due to the pandemic (during the COVID-19 phase) from March to Mai 2020 are compared in reference to their sample characteristics and their results in patient reported outcomes.There are no significant differences between the two observed time periods in reference to the sociodemographic characteristics of the rehabilitation inpatients. At the beginning of the rehabilitation there was no significant difference in the scale somatization. There was a significantly higher score in the scales' anxiety and depression during the COVID-19 phase, but only to the extent of a small effect. The results of the scales of activity and participation (ICF 3 F AT) as well as functionality (WHODAS 2.0) do not differ in the time periods at the beginning of the rehabilitation. However, rehabilitation inpatients with low socioeconomic status (rehabilitation allowance or disability pension) have critical scores in some scales. The rehabilitation success is comparable to the one before the COVID-19 pandemic and falls within the range of medium to high effect sizes.The study shows - with respect to its limitations - low or no significant differences in reference to the sociodemographic data and the symptomatic load at the beginning of the rehabilitation. The effect sizes are comparable with the time frame bevor the COVID-19 pandemic. The results of international studies, which reported a considerable increase in psychological stress of the population cannot directly be transferred to the Austrian rehabilitation clientele.In der internationalen Literatur werden Steigerungen der Inzidenzraten psychischer Erkrankungen durch die COVID-19-Pandemie berichtet. Junge Menschen und Menschen mit psychischen Vorerkrankungen sind besonders durch die Pandemie belastet. Gegenstand dieser Studie sind das Ausmaß psychischer Symptombelastung, die Funktionsfähigkeit und der Behandlungserfolg bei Rehabilitanden der medizinisch-psychiatrischen Rehabilitation im Jahr vor Beginn der COVID-19-Pandemie und während der COVID-19-Phase.Die Daten von N=1715 Rehabilitanden mit Reha-Abschluss vor dem ersten Lockdown und von N=707 Rehabilitanden mit Reha-Beginn nach der Corona-bedingten Schließung der Klinik von März bis Mai 2020 aus den Jahren 2019 und 2020 werden hinsichtlich der Stichprobencharakteristik sowie der Ergebnisse in den Patient-reported Outcomes (Beginn und Ende der Rehabilitation) verglichen.Zwischen den beiden Beobachtungszeiträumen zeigen sich keine bedeutsamen Unterschiede in der soziodemografischen Charakteristik der Rehabilitanden. Bei Reha-Beginn zeigt sich in der Skala Somatisierung kein signifikanter Unterschied, in den Skalen Ängstlichkeit und Depressivität zeigt sich während der COVID-19-Phase ein signifikant höherer Wert, allerdings im Ausmaß eines sehr kleinen Effekts. In den Skalen zu Aktivitäten und Teilhabe (ICF 3 F AT) sowie bei der Funktionsfähigkeit (WHODAS 2.0) unterscheiden sich die Werte der Vergleichszeiträume bei Reha-Beginn nicht. Rehabilitanden mit niedrigerem sozioökonomischem Status (Reha-Geld oder Invaliditäts-/Berufsunfähigkeitspension) weisen hingegen in einigen Skalen kritischere Werte auf. Der Reha-Erfolg ist vergleichbar mit dem Zeitraum vor der COVID-19-Pandemie und liegt im Bereich von mittleren bis hohen Effektgrößen.Die Studie zeigt – unter Berücksichtigung der Limitationen – geringe oder gar keine signifikanten Unterschiede in den soziodemografischen Daten und in der Symptombelastung bei Reha-Beginn und die Effektgrößen sind vergleichbar mit dem Zeitraum vor der COVID-19-Pandemie. Die Ergebnisse internationaler Studien, dass es zu einem deutlichen Anstieg psychischer Belastungen während der COVID-19-Pandemie in der Bevölkerung gekommen ist, können nicht direkt auf die österreichische Reha-Klientel übertragen werden.

Resistance towards cancer treatment represents a major clinical obstacle, preventing cure of cancer patients. To gain mechanistic insights, we developed a model for acquired resistance to chemotherapy by treating mice carrying patient derived xenografts (PDX) of acute lymphoblastic leukemia with widely-used cytotoxic drugs for 18 consecutive weeks. In two distinct PDX samples, tumors initially responded to treatment, until stable disease and eventually tumor re-growth evolved under therapy, at highly similar kinetics between replicate mice. Notably, replicate tumors developed different mutations in TP53 and individual sets of chromosomal alterations, suggesting independent parallel clonal evolution rather than selection, driven by a combination of stochastic and deterministic processes. Transcriptome and proteome showed shared dysregulations between replicate tumors providing putative targets to overcome resistance. In vivo CRISPR/Cas9 dropout screens in PDX revealed broad dependency on BCL2, BRIP1 and COPS2. Accordingly, venetoclax re-sensitized derivative tumors towards chemotherapy, despite genomic heterogeneity, demonstrating direct translatability of the approach. Hence, despite the presence of multiple resistance-associated genomic alterations, effective rescue treatment for polychemotherapy-resistant tumors can be identified using functional testing in preclinical models.

Glioblastoma (GBM) is a non-T-cell–inflamed cancer characterized by an immunosuppressive microenvironment that impedes dendritic cell maturation and T-cell cytotoxicity. Proangiogenic cytokines such as VEGF and angiopoietin-2 (Ang-2) have high expression in glioblastoma in a cell-specific manner and not only drive tumor angiogenesis and vascular permeability but also negatively regulate T-lymphocyte and innate immune cell responses. Consequently, the alleviation of immunosuppression might be a prerequisite for successful immune checkpoint therapy in GBM. We here combined antiangiogenic and immune checkpoint therapy and demonstrated improved therapeutic efficacy in syngeneic, orthotopic GBM models. We observed that blockade of VEGF, Ang-2, and programmed cell death protein-1 (PD-1) significantly extended survival compared with vascular targeting alone. In the GBM microenvironment, triple therapy increased the numbers of CTLs, which inversely correlated with myeloid-derived suppressor cells and regulatory T cells. Transcriptome analysis of GBM microvessels indicated a global vascular normalization that was highest after triple therapy. Our results propose a rationale to overcome tumor immunosuppression and the current limitations of VEGF monotherapy by integrating the synergistic effects of VEGF/Ang-2 and PD-1 blockade to reinforce antitumor immunity through a normalized vasculature.

Genetic factors were shown to play a major role in both variation of treatment response and incidence of adverse effects to medication in affective disorders. Nevertheless, there is still a lack of therapygenetic studies, investigating the prediction of psychological therapy outcomes from genetic markers. Neuroplasticity and one of its mediators, brain-derived neurotrophic factor (BDNF), are potential research targets in this field. We aimed to investigate Tag SNP polymorphisms of the BDNF gene in depressed patients treated with cognitive behavioral therapy (CBT) in the context of a standardized 6-weeks outpatient rehabilitation program. Treatment response was assessed calculating the mean differences in BDI-II (Beck Depression Inventory) scores from admission to discharge. Six BDNF SNPs, including the Val66Met polymorphism (rs6265), were genotyped. Both genotypic data and BDI-II-scores at admission and discharge were available for 277 patients. Three SNPs, rs10501087 (p = 0.005, FDRp=0.015), rs11030104 (p = 0.006, FDRp=0.012), and the Val66Met polymorphism (rs6265, p0.001, FDRp=0.006), were significantly associated with treatment response in depressed patients, even after multiple testing correction using the false discovery rate method (FDRp). We conclude that BDNF might serve as promising genetic marker for treatment response to psychological treatment in depression. However, due to our limited sample size, further studies are needed to disentangle the role of BDNF as potential therapygenetic marker.

Background Oxytocin (OXT) is a neuropeptide and hormone involved in emotional functioning and also seems to play a role in moderating the stress response. Both preclinical and clinical studies point to an increased methylation status of the Oxytocin receptor (OXTR) promoter region with concomitant deficits in social, cognitive and emotional functioning. We hypothesize that methylation levels (%) of the oxytocin receptor promoter region correlate with the severity of depression symptoms and/or with the severity of childhood trauma within this present sample of affective disorder patients. Methodology Eight hundred forty six (846) affective disorder patients of Central European origin were recruited at the Department of Psychiatry and Psychotherapy of the Medical University Vienna, the Karl Landsteiner University for Health and Science and Zentren für seelische Gesundheit, BBRZ-Med Leopoldau. Psychiatric assessment included a semi-structured diagnostic interview (Schedules for Clinical Assessment in Neuropsychiatry), the Hamilton Depression Scale and the Childhood Trauma Questionnaire. Concomitantly DNA samples of peripheral blood cells were collected for Multiplexed and Sensitive DNA Methylation Testing. Results Our data suggests a positive but not significant association between OXTR promoter Exons 1–3 methylation levels and severity of depression symptoms as well as severity of emotional neglect in affective disorder patients and no association with childhood trauma. Conclusions Our findings contribute to elucidate the role of OXTR in affective disorders, but further longitudinal studies in particular are necessary to broaden the current state of knowledge.

Minimally invasive oesophagectomy (MIO) for oesophageal cancer may reduce surgical complications compared with open oesophagectomy. MIO is, however, technically challenging and may impair optimal oncological resection. The aim of the present study was to assess if MIO for cancer is beneficial.A systematic literature search in MEDLINE, Web of Science and CENTRAL was performed and randomized controlled trials (RCTs) comparing MIO with open oesophagectomy were included in a meta-analysis. Survival was analysed using individual patient data. Random-effects model was used for pooled estimates of perioperative effects.Among 3219 articles, six RCTs were identified including 822 patients. Three-year overall survival (56 (95 per cent c.i. 49 to 62) per cent for MIO versus 52 (95 per cent c.i. 44 to 60) per cent for open; P = 0.54) and disease-free survival (54 (95 per cent c.i. 47 to 61) per cent versus 50 (95 per cent c.i. 42 to 58) per cent; P = 0.38) were comparable. Overall complication rate was lower for MIO (odds ratio 0.33 (95 per cent c.i. 0.20 to 0.53); P 0.010) mainly due to fewer pulmonary complications (OR 0.44 (95 per cent c.i. 0.27 to 0.72); P 0.010), including pneumonia (OR 0.41 (95 per cent c.i. 0.22 to 0.77); P 0.010).MIO for cancer is associated with a lower risk of postoperative complications compared with open resection. Overall and disease-free survival are comparable for the two techniques.Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

Objectives To measure mentalization in a feasible manner, various instruments have been designed in recent years. The Brief Reflective Functioning Interview (BRFI) is a short interview that is based on the Adult Attachment Interview (AAI). The aim of both studies was to examine the psychometric properties of the German version of the BRFI and to compare them to those of the AAI. Methods In Study 1, we examined 60 students using the BRFI and the AAI. In Study 2, the validity of the BRFI was examined using a mixed sample of students and patients (N = 149). Trained coders evaluated the Reflective Functioning Scale (RFS) for the BRFI and the AAI. Results We found a significant positive correlation between the RFS total scores of the BRFI and those of the AAI. In addition, both interviews showed excellent internal consistency. We could also show that persons with mental disorders exhibit lower levels of RF score than mentally stable individuals. Women had higher RF scores in the BRFI than men in both samples. Persons whose mentalization capacity was rated below average in either the BRFI or the AAI also reported significantly lower mentalization ability in the self-assessment (p Conclusions Our results revealed that the RFS scores measured by the BRFI are highly comparable to those measured by the AAI. Our findings support the results of previous studies, suggesting that the BRFI is a reliable, valid and easy-to-administer alternative to the AAI. Practitioner points The German version of the Brief Reflective Functioning Interview (BRFI) proved to be a reliable and valid instrument for the assessment of reflective functioning that is shorter in terms of time to complete and the evaluation process than the measurement via the Adult Attachment Interview (AAI). Reflective functioning is negatively associated with psychopathology.

Transposable elements (TEs) promote genetic innovation but also threaten genome stability. Despite multiple layers of host defence, TEs actively shape mammalian-specific developmental processes, particularly during pre-implantation and extra-embryonic development and at the maternal-fetal interface. Here, we review how TEs influence mammalian genomes both directly by providing the raw material for genetic change and indirectly via co-evolving TE-binding Krüppel-associated box zinc finger proteins (KRAB-ZFPs). Throughout mammalian evolution, individual activities of ancient TEs were co-opted to enable invasive placentation that characterizes live-born mammals. By contrast, the widespread activity of evolutionarily young TEs may reflect an ongoing co-evolution that continues to impact mammalian development.

Preliminary evidence suggests that biased attention could be crucial infostering the emotion recognition abnormalities in borderline personalitydisorder (BPD). We compared BPD patients to Cluster-C personality disorder (CC) patients and non-patients (NP) regarding emotion recognition inambiguous faces and their visual attention allocation to the eyes. The roleof comorbid posttraumatic stress disorder (PTSD) in BPD regarding emotion recognition and visual attention was explored. BPD patients fixated theeyes of angry/happy, sad/happy, and fearful/sad blends longer than nonpatients. This visual attention pattern was mainly driven by BPD patientswith PTSD. This subgroup also demonstrated longer fixations than CCpatients and a trend towards longer fixations than BPD patients withoutPTSD for the angry/happy and fearful/sad blends. Emotion recognition wasnot altered in BPD. Biased visual attention towards the eyes of ambiguousfacial expressions in BPD might be due to trauma-related attentional biasrather than to impairments in facial emotion recognition.

BACKGROUND In diffuse WHO grade II gliomas (LGG), the extent of resection (EOR) required to achieve significant survival benefits remains elusive. OBJECTIVE To evaluate the association of residual volume (RV) and EOR with progression-free survival (PFS) or overall survival (OS) in LGG in a retrospective, multicenter series by the German study group of intraoperative MRI (GeSGIM). METHODS Consecutive cases were retrospectively assessed from 5 centers. Tumors were volumetrically quantified before and after surgery, and clinical data were analyzed, including IDH mutations and neurologic deficits. Kaplan-Meier estimates, accelerated failure time models (AFT), and multivariate Cox regression models were calculated to identify determinants of survival. RESULTS A total of 140 cases were analyzed. Gross total resection (GTR) was associated with significantly longer PFS compared to any incomplete resection (P = .009). A significant survival disadvantage was evident even for small (>0-5 ml) residuals and increased for moderate (>5-20 ml) and large remnants (>20 ml) P = .001). Accordingly, PFS increased continuously for 20% incremental steps of EOR (P

The surgical management of hydrocephalus in patients with posterior fossa lesions (PFL) is critical for optimal patient outcome(s). Accordingly, it is prudent to identify patients in need of aggressive surgical intervention (i.e., ventriculoperitoneal [VP] shunting). To analyze prevalence of, and risk factors associated with, the development of post-operative hydrocephalus in both pediatrics and adults. A retrospective institutional analysis and review of patient records in those who had undergone PFL surgery was performed. In so doing, the authors identified patients that went on to develop post-operative hydrocephalus. The study included pediatric and adult patients treated between 2009 and 2017. Fifteen of 40 pediatric (37.5%) and 18 of 262 adult (6.9%) patients developed hydrocephalus after PFL surgery. The most common tumor entity in pediatrics was medulloblastoma (34%), astrocytoma (24.4%), and pilocytic astrocytoma (22%), whereas in adults, metastasis (29.5%), meningioma (22%), and acoustic neuroma (17.8%) were most common. Young age ≤ 2 years, medulloblastoma (OR 13.9), and brain stem compression (OR 5.4) were confirmed as independent predictors for hydrocephalus in pediatrics and pilocytic astrocytoma (OR 15.4) and pre-operative hydrocephalus (OR 3.6) in adults, respectively. All patients received VP shunts for hydrocephalus management and the mean follow-up was 29.5 months in pediatrics vs 19.2 months in adults. Overall complication rates related to VP shunts were 33.3% in pediatrics and 16.7% in adults, respectively. Shunt dependency and associated complications in pediatrics were noted to be higher than in adults. Given the identification of predictors for hydrocephalus, it is authors' contention that certain patients with those predictors may ultimately benefit from an alternative treatment regimen (e.g., pre-operative interventions) prior to PFT surgery.

In natural orifice transluminal endoscopic surgery (NOTES) with transrectal (TR) access the intraoperative opening of the rectal wall poses a risk of intraperitoneal contamination and subsequent infectious complications. A rectal washout with a disinfectant may reduce this risk. The aim of the study was to assess the intraoperative contamination on the circular stapler pin when a rectal washout with povidone-iodine (RW-PI) or Ringer solution was performed in patients undergoing left-sided colectomy. Furthermore, the additional effect of an irrigation instrument on the contamination was evaluated.In a patient and assessor blinded randomized controlled trial, patients undergoing left-sided colectomy were assigned to rectal washout with PI with an irrigation instrument (RW-PI; n = 23), rectal washout with Ringer solution with an irrigation instrument (RW-R; n = 21) or rectal washout with Ringer solution without an irrigation instrument (RW; n = 25). An end-to-end anastomosis with a circular stapler was performed. The contamination on the pin of the circular stapler was chosen as primary endpoint in order to simulate the intraabdominal contamination risk during TR NOTES. Secondary endpoints were contamination of the rectal mucosa, peritoneal contamination and postoperative morbidity.The contamination rate of the pin of the circular stapler did not differ (RW-PI 39.1%, RW-R 33.3%, RW 52.0%; P = 0.421), but contamination of the rectal mucosa was reduced (47.8% versus 95.2% versus 100%; P 0.001) and peritoneal contamination tended to be reduced (39.1% versus 71.4% versus 60.0%; P = 0.09) when a rectal washout with PI was performed. The rates of infectious complications (17.4% versus 9.5% versus 12.0%; P = 0.821) and of overall complications (30.4% versus 28.6% versus 44.0%; P = 0.476) did not differ.Despite an intense rectal washout with PI, contamination of the stapler pin did not differ. Intraabdominal bacterial translocation was frequently encountered even after disinfectant rectal washout with PI. Further studies might focus on the clinical impact of intraabdominal contamination in TR NOTES.

Two adolescent boys presented with acute acneiform eruptions in the setting of recent dupilumab administration. Subsequent investigation via direct scraping of pustules revealed live Demodex mite colonization of the face. These adolescent patients represent a population not commonly associated with Demodex folliculitis, and we theorize their baseline commensal Demodex mite population may have increased as a consequence of dupilumab-induced, focused immunomodulation. We recommend that pediatricians consider Demodex potentially etiologic in patients presenting with new onset acneiform or rosacea-like dermatoses in patients treated with dupilumab.

Objective The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established. Methods We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology. Result In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families. Conclusions and Relevance The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.

Worker posture, task time and performance are often affected when one-handed manual dexterous tasks are performed in small overhead spaces under an obscured view. A common method used for supplementing visual feedback in these cases is a hand-held telescopic mirror, but that involves working with both arms extended overhead, and is often accompanied by awkward neck and shoulder postures. A video camera was considered as an alternative to using a mirror for visual feedback and reducing overhead reach. A mirror, a borescope and an omnidirectional camera were evaluated while laboratory participants performed three one-handed simulated manufacturing tasks in a small overhead enclosure. Videos were recorded for quantifying the time that postures were assumed while performing the tasks. The average time that both arms were above mid-shoulder height for the omnidirectional camera was more than 2.5 times less than for the mirror and borescope. The average proportion of neck strain time was 0.01% (or less) for both the omnidirectional camera and the borescope, compared to 83.68% for the mirror. No significant differences were observed in task completion times between the three modalities. Hence, an omnidirectional camera can provide visibility while reducing straining postures for manufacturing operations involving overhead work.

Due to the increasing age of patients, the evaluation of bone density is crucial, especially in preparation for spinal surgery. The aim of this study was to determine bone density using a computed tomography (CT) and to correlate Hounsfield units (HU) with bone density values of a quantitative computed tomography (QCT).The study is a monocentric, retrospective data analysis. We examined 902 vertebral bodies from a total of 369 patients who received a CT of the thoracolumbar spine in the period from 2015 to 2019 and compared the HU with values of a QCT. A general equation for calculation the QCT values was established.We found a significant correlation between the Hounsfield units and the corresponding QCT-values (r = 0.944, P0.001). We also demonstrated that the calculated QCT values are independent of patient sex (P0.942). Furthermore, we could not demonstrate differences in the correlation of the 3 measured levels (axial, sagittal, and coronary) to the QCT values. The QCT-values can be calculated on the basis of a native CT of the lumbar spine using the equation: QCT = 17.8 + 0.7 × HU.The equation allows calculating bone density values without the need for an additional QCT and without further radiation exposure or costs. With this measuring method it is possible to obtain additional information from a computed tomography.

Purpose: The extent of preoperative peritumoral edema in glioblastoma (GBM) has been negatively correlated with patient outcome. As several ongoing studies are investigating T-cell based immunotherapy in GBM, we conducted this study to assess whether peritumoral edema with potentially increased intracranial pressure, disrupted tissue homeostasis and reduced local blood flow has influence on immune infiltration and affects survival. Methods: A volumetric analysis of preoperative imaging (gadolinium enhanced T1 weighted MRI sequences for tumor size and T2 weighted sequences for extent of edema (including the infiltrative zone, gliosis etc.) was conducted in 144 patients using the Brainlab® software. Immunohistochemical staining was analyzed for lymphocytic- (CD 3+) and myelocytic (CD15+) tumor infiltration. A retrospective analysis of patient-, surgical-, and molecular characteristics was performed using medical records. Results: The edema to tumor ratio was neither associated with progression-free nor overall survival (p=0.90, p=0.74). However, GBM patients displaying IDH-1 wildtype had significantly higher edema to tumor ratio than patients displaying an IDH-1 mutation (p=0.01). Immunohistopathological analysis did not show significant differences in lymphocytic or myelocytic tumor infiltration (p=0.78, p=0.74) between these groups. Conclusion: In our cohort, edema to tumor ratio had no significant correlation with immune infiltration and outcome. However, patients with an IDH-1wildtype GBM had a significantly higher edema to tumor ratio compared to their IDH-1 mutated peer group. Further studies are necessary to elucidate the underlying mechanisms.

Objective As shown in a previous study, aneurysm location seems to influence prognosis in patients with subarachnoid hemorrhage (SAH). We compared patients with ruptured aneurysms of anterior and posterior circulation, undergoing coil embolization, concerning differences in outcome and prognostic factors. Methods Patients with SAH were entered into a prospectively collected database. We retrospectively identified 307 patients with aneurysms of the anterior circulation (anterior cerebral artery, carotid bifurcation, and middle cerebral artery) and 244 patients with aneurysms of the posterior circulation (aneurysms of the basilar artery, posterior inferior cerebellar artery, posterior communicating artery and posterior cerebral artery). All patients underwent coil embolization. The outcome was assessed using the modified Rankin Scale (mRS; favorable [mRS 0–2] vs. unfavorable [mRS 3–6]) 6 months after SAH. Results In interventionally treated aneurysms of the anterior and posterior circulation, statistically significant risk factors for poor outcome were worse admission status and severe cerebral vasospasm. If compared with patients with ruptured aneurysms of the anterior circulation, patients with aneurysms of the posterior circulation had a significantly poorer admission status, and suffered significantly more often from an early hydrocephalus. Nonetheless, there were no differences in outcome or mortality rate between the two patient groups. Conclusion Patients with a ruptured aneurysm of the posterior circulation suffer more often from an early hydrocephalus and have a significantly worse admission status, possibly related to the untreated hydrocephalus. Nonetheless, the outcome and the mortality rate were comparable between ruptured anterior and posterior circulation aneurysms, treated by coil embolisation. Therefore, despite the poorer admission status of patients with ruptured posterior circulation aneurysms, treatment of these patients should be considered.