Improvements in Pediatric Bone Loss Reconstruction With the Induced Membrane Technique.

BACKGROUND: The induced membrane technique is now widely used for pediatric diaphyseal bone loss due to various etiologies. Although consolidation rates remain satisfactory, complications, and healing delays may occur requiring additional procedures. We studied a series of induced membrane bone reconstructions in which the second stage included an embedded endomembranous non vascularized fibular shaft, in addition to iliac bone grafts. The purpose of this study was to analyze the results in terms of bone consolidation and complications. METHODS: This is a retrospective comparative and multicentric study of 32 children with large bone loss treated with the induced membrane reconstruction technique. Patients were divided into 2 groups according to the graft used during the second stage. The first group (G1) of 16 patients had a nonvascularized fibula embedded inside the membrane in addition with the corticocancellous grafts from the iliac crest. The second group (G2) of 16 patients underwent reconstruction using the original technique, with iliac crest graft only. RESULTS: The 2 groups were similar in terms of etiologies of bone loss and follow-up (mean: 44 mo for G1 and 49 mo for G2). Mean bone losses were 15.4 cm (range: 2 to 25; SD: 5.6) for G1 and 10.6 cm (range: 3 to 19; SD: 5.2) for G2. In the first group, all patients healed primarily, with a mean time of 5.9 months (range: 4 to 8; SD: 1.6). In the second group, 2 of 16 patients did not healed; for the others 14, healing mean time was 6.9 months (range: 3 to 12; SD: 2.7). The short-term and long-term complications rates were 38% to 19% for G1 and 50% to 31% for G2, respectively. Regarding the donor site, the fibulas reconstructed spontaneously with a mean time of 4.8 months (range: 3 to 6; SD: 1.2). CONCLUSIONS: The integration of a nonvascularized fibula during the second stage of the induced membrane technique appears to improve the consolidation rate in the pediatric population. LEVEL OF EVIDENCE: Level III-Retrospective comparative study.

Timing Matters: Optimizing the Timeframe for Preoperative Weight Loss to Mitigate Postoperative Infection Risks in Total Knee Arthroplasty.

BACKGROUND: We explore the incidence of periprosthetic infections post-total knee arthroplasty (TKA) in morbidly obese patients who achieved weight loss. Current American Academy of Orthopaedic Surgeons guidelines suggest a preoperative body mass index (BMI) below 40 for TKA. This study assesses infection risks in patients initially who had a BMI of 40-50 who reduced their BMI to under 35 at varying intervals prior to surgery. METHODS: We reviewed a national, all-payer database, PearlDiver, for patients undergoing primary TKA. Patients were stratified based on initial BMI of 40 to 50 and reduction of BMI to less than 35 at 3 months (n = 1,932), 3 to 6 months (n = 794), 6 to 9 months (n = 2,233), and 9 to 12 months (n = 1,194) prior to TKA, as well as patients who had a BMI between 40 to 50 (n = 41,632) on the day of surgery. The nonobese group comprised of patients who had a BMI between 20 and 30 (n = 33,294). Multivariate analyses were performed at one-year follow-up. RESULTS: We found an increased risk of PJI for patients who had achieved BMI reduction less than nine months prior to TKA, compared to the BMI 20 to 30 cohort at the one-year follow-up (P < .001). Patients who achieved BMI reduction nine to twelve months prior to TKA showed no significant difference in PJI risk compared to the matching nonobese cohort at one-year follow-up (P = .400). CONCLUSIONS: In conclusion, our results suggest that weight loss should be achieved at least nine months before TKA to decrease infection risks. These findings have significant implications for surgical considerations in obese patients undergoing TKA.

Thematic analysis of online discussion forums for soft tissue sarcomas.

BACKGROUND AND OBJECTIVES: As there is an increasing reliance on the internet for medical information, patients diagnosed with rare diseases have turned to online community forums to share information about their diagnoses. These forums help patients to gather and share information about their experience with disease. Additionally, these platforms enable patients to build unique connections based on their shared experiences. The objective of this study was to review shared posts in online community forums by individuals with soft tissue sarcomas to better understand commonly discussed themes. This information may improve the physicians' understanding of patients' concerns and feelings at the time of diagnosis and treatment. METHODS: We entered "sarcoma discussion forum" in search engines to identify internet discussion boards. Four major discussion forums were analyzed, and posts written between January 1, 2017 through May 1, 2022 addressing soft tissue sarcomas present in the upper and lower extremities were collected. Each post was analyzed by the two investigators in three steps (open coding, axial coding, and selective coding). RESULTS: A total of 506 posts were included in the final analysis. We used twenty-seven axial codes and four selective codes. Emotional Aspects/Connecting with Others was the most common theme (77 % of posts) followed by Information Support: Treatment (38 % of posts), Information Support: Diagnosis (24 % of posts) and Information Support: Recovery (21 % of posts). CONCLUSIONS: The most prevalent theme was centered on emotional aspects of these patients' journeys, highlighting the importance of providing resources to address emotional support for patients with soft tissue sarcoma and their families. LEVEL IV: Qualitative research study.

Most Patients With Bone Sarcomas Seek Emotional Support and Information About Other Patients' Experiences: A Thematic Analysis.

BACKGROUND: Online discussion forums allow individuals who otherwise may be strangers to create a community where they can seek and share information. Patients with bone sarcomas and their support networks use discussion forums dedicated to cancer support. There is a paucity of published reports regarding the care experience of patients with bone sarcomas because studies on online discussion groups have primarily focused on some of the more common cancers, including breast and prostate cancer. Understanding commonly discussed themes among patients with bone sarcomas would allow treating physicians to have a better understanding of patient concerns when providing patient education and counseling. QUESTION/PURPOSE: We performed this study to review posts from bone sarcoma internet discussion boards to establish common themes related to the care experience of patients with sarcomas. METHODS: Online discussion forums were identified using the search term "sarcoma discussion forum." After identifying 12 websites, we excluded closed forum groups, websites with missing or invalid links to forums, and nonpublic forums, such as groups on Facebook. These websites include profiles and photos that are personal, and sufficient author anonymity could not be achieved for this study. Posts written between January 1, 2012, and May 1, 2022, posted on five discussion boards were reviewed and collected until we reached a point of data saturation in which we agreed that the collection of additional posts would not reveal new themes. Discussion threads were filtered to identify posts pertaining to the most common bone sarcomas: chondrosarcoma, Ewing sarcoma, and osteosarcoma. Grounded theory-the methodology of repeated analyses of qualitative data to identify recurring themes or concepts-was used to analyze posts. Caregiver posts were delineated from patient posts and categorized separately for subgroup analysis. Grounded theory, although a qualitative method, endeavors to integrate the strengths inherent in quantitative methods with qualitative approaches. Grounded theory categorizes words, language, and the meanings these imply and seeks to organize and reduce the data gathered into themes or essences, which, in turn, can be fed into descriptions, models, or theories. Our analysis used three reviews of text to assign and group codes based on repeating ideas or concepts. The first review (open coding) aims to assign codes based on the verbatim text included by the author to capture the specific thoughts and ideas of the post. The second review (axial coding) aims to consolidate the ideas of posts by applying broader concepts to each post. The third and final review (selective coding) aims to further consolidate the themes of each post by trying to embody the main message contained in a post. A total of 570 posts from 139 threads were collected and analyzed using grounded theory. Twenty-five axial codes and four selective codes were created. We defined data saturation by the absence of a new open code in the analysis of a block of 50 posts to ensure that signals of saturation were not accepted too early in the analysis. RESULTS: The four selective codes included emotional aspects or connecting with others, information support: diagnosis, information support: treatment, and information support: recovery. Of these four codes, emotional aspects and connecting with others was the most prevalent theme (78% [445 of 570] of posts) followed by information support: treatment (49% [282 of 570] of posts). Information support: diagnosis and information support: recovery were each captured in 15% of posts. CONCLUSION: Analysis of posts reveals that the two most common themes involve seeking out emotional support and information about the experiences of others with various treatment modalities. Although most of the posts we assessed contained experiential information and emotional support rather than directed medical advice, future studies should assess the accuracy of information shared among online sarcoma forums. CLINICAL RELEVANCE: Physicians caring for patients with sarcomas should not only address patient concerns related to medical care, but also provide emotional support directly and assist patients by providing resources to peer support outlets, including online discussion forums. Although we cannot ascertain the proportion of patients who use online sites given the anonymity of posts included, these findings suggest common experiential themes across patients with sarcomas outside their doctors' offices. It is important that providers be aware of reputable forums to provide as resources for their patients. The Musculoskeletal Tumor Society may further benefit from endorsing one or more of these forums and providing physician oversight to monitor misinformation.

Pregabalin does not reduce postoperative pain after outpatient ACL surgery: A case-control study.

INTRODUCTION: In France, prescribing pregabalin requires a secure prescription valid for 6 months since the decree of 12 February 2021, based on recommendations of the French Centre for Evaluation and Information on Pharmacodependence and Addiction vigilance (CEIP-A). This led to discontinuation of this treatment as a postoperative analgesic in the French ACL Study (FAST) cohort. We aimed to evaluate the impact of this change on early postoperative pain. HYPOTHESIS: Pregabalin is an important analgesic for reducing early postoperative pain after anterior cruciate ligament (ACL) repair. METHODS: At our healthcare facility, 584 patients from the FAST cohort who underwent primary isolated ACL reconstruction were included: 292 patients operated before June 1, 2021 who received pregabalin postoperatively and 292 patients operated after June 1, 2021 who did not receive pregabalin. The patients were matched based on age, sex, preoperative Lysholm and Tegner scores. Pain was evaluated on a visual analog scale (VAS) on D0 in the evening, D0 at night, D1, D2 and D3. RESULTS: The patients who did not receive pregabalin had more severe pain at night on D0: 5.21 vs 5.68 (p=.048). There was no difference between groups in the postoperative pain at rest during the evening of D0 (p=.89), D1 (p=.33), D2 (p=.37) and D3 (p=.21). CONCLUSION: In the context of outpatient arthroscopic ACL reconstruction, pregabalin does not reduce early postoperative pain in a clinically significant manner. LEVEL OF EVIDENCE: IV; case-control study.

Research Data Management and Data Sharing for Reproducible Research-Results of a Community Survey of the German National Research Data Infrastructure Initiative Neuroscience.

Science is changing: the volume and complexity of data are increasing, the number of studies is growing and the goal of achieving reproducible results requires new solutions for scientific data management. In the field of neuroscience, the German National Research Data Infrastructure (NFDI-Neuro) initiative aims to develop sustainable solutions for research data management (RDM). To obtain an understanding of the present RDM situation in the neuroscience community, NFDI-Neuro conducted a comprehensive survey among the neuroscience community. Here, we report and analyze the results of the survey. We focused the survey and our analysis on current needs, challenges, and opinions about RDM. The German neuroscience community perceives barriers with respect to RDM and data sharing mainly linked to (1) lack of data and metadata standards, (2) lack of community adopted provenance tracking methods, (3) lack of secure and privacy preserving research infrastructure for sensitive data, (4) lack of RDM literacy, and (5) lack of resources (time, personnel, money) for proper RDM. However, an overwhelming majority of community members (91%) indicated that they would be willing to share their data with other researchers and are interested to increase their RDM skills. Taking advantage of this willingness and overcoming the existing barriers requires the systematic development of standards, tools, and infrastructure, the provision of training, education, and support, as well as additional resources for RDM to the research community and a constant dialogue with relevant stakeholders including policy makers to leverage of a culture change through adapted incentivization and regulation.

Is the Repair of Acute Scapholunate Injuries Associated With Distal Radius Fractures Necessary at the Time of Osteosynthesis? A Systematic Review and Meta-Analysis.

BACKGROUND: Acute scapholunate ligament injuries (SLIs) can occur in distal radial fractures (DRFs). This systematic review compares patient-reported outcomes and range of motion (ROM) between operative and nonoperative treatment of acute SLIs in association with surgical fixation of DRFs. We hypothesize that there is no clinical difference. METHODS: A meta-analysis was used to evaluate the effectiveness of SLI repair versus no repair occurring with DRF with Disabilities of the Arm, Shoulder, and Hand (DASH) scores. We identified 154 articles of which 14 were eligible for review. Only 7 studies reported sufficient radiographic or clinical outcomes data and were included: 3 for meta-analysis and 4 underwent narrative analysis due to lack of homogeneity. We analyzed the patients in 2 groups: operative SLI (O-SLI) versus nonoperative SLI (NO-SLI). The primary outcomes were ROM and DASH scores with 1-year follow-up, where a pooled effect size was generated to determine a difference between groups. RESULTS: A total of 128 patients were included (71 O-SLI and 57 NO-SLI), with a mean follow-up of 70.2 months (SD: 23.5). The overall effect size for ROM for flexion was 1.74 (95% confidence interval [CI], -3.48 to 6.95; P = .51) and for extension was 0.79 (95% CI, -3.41 to 4.99; P = .71), while the overall effect size for DASH scores was -0.28 (95% CI, -0.66 to 0.10; P = .14). Although NO-SLI led to better ROM and O-SLI led to lower DASH scores, these were not significantly different. CONCLUSION: The acute surgical intervention of a scapholunate interosseous ligament injury is no different from conservative management in the setting of acute DRFs undergoing osteosynthesis. But the sample size for pooed analyses was small, hence the evidence to date is low to recommend either way.

Age-Related Hearing Loss, Neuropsychological Performance, and Incident Dementia in Older Adults.

BACKGROUND: Age-related hearing loss (HL) has been associated with dementia, though the neurocognitive profile of individuals with HL is poorly understood. OBJECTIVE: To characterize the neurocognitive profile of HL. METHODS: N = 8,529 participants from the National Alzheimer's Coordinating Center ≥60 years and free of cognitive impairment who were characterized as Untreated-, Treated-, or No HL. Outcomes included executive function (Trail Making Test [TMT] Part B), episodic memory (Immediate/Delayed Recall), language fluency (Vegetables, Boston Naming Test), and conversion to dementia. Regression models were fit to examine associations between HL and neurocognitive performance at baseline. Cox proportional hazards models examined the links between HL, neurocognitive scores, and development of dementia over follow-up. RESULTS: At baseline, those with Untreated HL (versus No HL) had worse neurocognitive performance per standardized difference on executive function (TMT Part B [mean difference = 0.05 (95% CI 0.00, 0.10)]) and language fluency (Vegetables [mean difference = -0.07 (95% CI -0.14, -0.01)], Boston Naming Test [mean difference = -0.07 (95% CI -0.13, -0.01)]). No differences in these neurocognitive performance scores were demonstrated between Treated HL and No HL groups other than MMSE [mean difference = -0.06 (95% CI -0.12, 0.00)]. Through follow-up, executive dysfunction differed by hearing group (χ2(2) = 46.08, p < 0.0001) and was present among 39.12% in No HL, 44.85% in Untreated HL, and 49.40% in Treated HL. Worse performance across all cognitive domains predicted incident dementia. CONCLUSION: The observed association between Untreated HL and lower cognitive ability that improved when hearing aids were worn may reflect an inability to hear the test instructions. Future studies using cognitive assessments validated for use in HL are needed to evaluate the neuropsychological profile of HL and identify individuals at risk for dementia.

Prototypical Clinical Trial Registry Based on Fast Healthcare Interoperability Resources (FHIR): Design and Implementation Study.

BACKGROUND: Clinical trial registries increase transparency in medical research by making information and results of planned, ongoing, and completed studies publicly available. However, the registration of clinical trials remains a time-consuming manual task complicated by the fact that the same studies often need to be registered in different registries with different data entry requirements and interfaces. OBJECTIVE: This study investigates how Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) may be used as a standardized format for exchanging and storing clinical trial records. METHODS: We designed and prototypically implemented an open-source central trial registry containing records from university hospitals, which are automatically exported and updated by local study management systems. RESULTS: We provided an architecture and implementation of a multisite clinical trials registry based on HL7 FHIR as a data storage and exchange format. CONCLUSIONS: The results show that FHIR resources establish a harmonized view of study information from heterogeneous sources by enabling automated data exchange between trial centers and central study registries.

Frailty Worsens Antidepressant Treatment Outcomes in Late Life Depression.

OBJECTIVE: To investigate the relationship between frailty and treatment response to antidepressant medications in adults with late life depression (LLD). METHODS: Data were evaluated from 100 individuals over age 60 years (34 men, 66 women) with a depressive diagnosis, who were assessed for frailty at baseline (characteristics include gait speed, grip strength, activity levels, fatigue, and weight loss) and enrolled in an 8-week trial of antidepressant medication followed by 10 months of open-treatment. RESULTS: Frail individuals (n = 49 with ≥3 deficits in frailty characteristics) did not differ at baseline from the non/intermediate frail (n = 51 with 0-2 deficits) on demographic, medical comorbidity, cognitive, or depression variables. On average, frail individuals experienced 2.82 fewer Hamilton Rating Scale for Depression (HRSD) points of improvement (t = 2.12, df 89, p = 0.037) than the non/intermediate frail over acute treatment, with this difference persisting over 10 months of open-treatment. Weak grip strength and low physical activity levels were each associated with decreased HRSD improvement, and lower response and remission rates over the course of the study. Despite their poorer outcomes, frail individuals received more antidepressant medication trials than the non/intermediate frail. CONCLUSION: Adults with LLD and frailty have an attenuated response to antidepressant medication and a greater degree of disability compared to non/intermediate frail individuals. This disability and attenuated response remain even after receiving a greater number of antidepressant medication trials. Future research must focus on understanding the specific pathophysiology associated with the frail-depressed phenotype to permit the design and implementation of precision medicine interventions for this high-risk population.

Impact of smoking and fetal gender on preterm delivery.

According to the World Health Organization, smoking is the most important risk factor for adverse pregnancy outcomes in industrialized nations. We aimed to establish how fetal gender and smoking interact with regard to perinatal outcomes, especially preterm delivery. Data from 220,339 singleton pregnancies, obtained from the German Perinatal Survey in Schleswig-Holstein and registered between 2004 and 2017 were analyzed in regard to smoking behavior, fetal gender, and preterm delivery. The rate of preterm births was directly proportional to the women's consumption of nicotine. The rate of preterm deliveries was 6.8% among nonsmokers, and 13.2% in women who were very heavy smokers (≥22 cigarettes/day). Very heavy smoking (≥22 cigarettes/day) had a marked impact on extremely preterm births (<28 weeks of gestation) and very preterm births (28-31 weeks of gestation). Preterm births increased by 1.2% from heavy smokers to very heavy smokers; the differences between the other groups ranged between 0.1% and 0.4%. Fetal gender also had an impact on preterm birth: male infants were predominant in nearly all groups of women who delivered preterm infants. Smoking during pregnancy and male gender are both risk factors for preterm delivery. Fetal gender should be given greater attention as one of the several risk factors of preterm birth. Due to the high rate of morbidity among preterm infants and enormous costs for the healthcare system, women should be encouraged to cease or at least reduce smoking during pregnancy.

Age-Related Hearing Loss, Late-Life Depression, and Risk for Incident Dementia in Older Adults.

BACKGROUND: Hearing loss (HL), late-life depression, and dementia are 3 prevalent and disabling conditions in older adults, but the interrelationships between these disorders remain poorly understood. METHODS: N = 8529 participants ≥60 years who were free of cognitive impairment at baseline were analyzed from National Alzheimer's Coordinating Center Uniform Data Set. Participants had either No HL, Untreated HL, or Treated HL. Primary outcomes included depression (15-item Geriatric Depression Scale ≥5) and conversion to dementia. A longitudinal logistic model was fit to examine the association between HL and changes in depressive symptoms across time. Two Cox proportional hazards models were used to examine HL and the development of dementia: Model A included only baseline variables and Model B included time-varying depression to evaluate for the direct effect of changes in depression on dementia over time. RESULTS: Treated HL (vs no HL) had increased risk for depression (odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.04-1.54, p = .02) and conversion to dementia (hazard ratio [HR] = 1.29, 95% CI = 1.03-1.62, p = .03). Baseline depression was a strong independent predictor of conversion to dementia (HR = 2.32, 95% CI = 1.77-3.05, p < .0001). Development/persistence of depression over time was also associated with dementia (HR = 1.89, 95% CI = 1.47-2.42, p < .0001), but only accounted for 6% of the direct hearing-dementia relationship (Model A logHR = 0.26 [SE = 0.12] to Model B logHR = 0.24 [SE = 0.12]) suggesting no significant mediation effect of depression. CONCLUSIONS: Both HL and depression are independent risk factors for eventual conversion to dementia. Further understanding the mechanisms linking these later-life disorders may identify targets for early interventions to alter the clinical trajectories of at-risk individuals.

The ankle ligament reconstruction-return to sport after injury (ALR-RSI) is a valid and reproducible scale to quantify psychological readiness before returning to sport after ankle ligament reconstruction.

PURPOSE: Chronic ankle instability is the main complication of ankle sprains and requires surgery if non-operative treatment fails. The goal of this study was to validate a tool to quantify psychological readiness to return to sport after ankle ligament reconstruction. METHODS: The form was designed like the anterior cruciate ligament-return to sport after injury scale and "Knee" was replaced by the term "ankle". The ankle ligament reconstruction-return to sport after injury (ALR-RSI) scale was filled by patients who underwent ankle ligament reconstruction and were active in sports. The scale was then validated according to the international COSMIN methodology. The AOFAS and Karlsson scores were used as reference questionnaires. RESULTS: Fifty-seven patients (59 ankles) were included, 27 women. The ALR-RSI scale was strongly correlated with the Karlsson score (r = 0.79 [0.66-0.87]) and the AOFAS score (r = 0.8 [0.66-0.87]). A highly significant difference was found in the ALR-RSI between the subgroup of 50 patients who returned to playing sport and the seven who did not: 68.8 (56.5-86.5) vs 45.0 (31.3-55.8), respectively, p = 0.02. The internal consistency of the scale was high (α = 0.96). Reproducibility of the test-retest was excellent (ρ = 0.92; 95% CI [0.86-0.96]). CONCLUSION: The ALR-RSI is a valid, reproducible scale that identifies patients who are ready to return to the same sport after ankle ligament reconstruction. This scale may help to identify athletes who will find sport resumption difficult. LEVEL OF EVIDENCE: III.

A pilot randomized controlled trial of hearing aids to improve mood and cognition in older adults.

OBJECTIVES: Age-related hearing loss (ARHL) is a prevalent condition associated with increased risk for depression and cognitive decline. This 12-week prospective, double-blind pilot randomized controlled trial (RCT) of hearing aids (HAs) for depressed older adults with ARHL evaluated the feasibility of a novel research design. METHODS/DESIGN: N = 13 individuals aged ≥60 years with Major Depressive Disorder or Persistent Depressive Disorder and at least mild hearing loss (pure tone average ≥ 30 dB) were randomized to receive full- (active) vs low-amplification (sham) HAs added to psychiatric treatment as usual. Duration of HA use in hours/day, adverse events frequency, attrition rate, and maintenance of the study blinding were the primary outcome measures. RESULTS: Compliance with HAs was excellent (>9 hours/day for both groups) and rates of adverse events and drop-outs did not differ between groups. Preliminary data demonstrated differential improvement for active vs sham HAs on hearing functioning (Hearing Handicap Inventory for the Elderly [nonparametric effect size (np-ES) = 0.62]), depressive symptoms (Inventory for Depressive Symptomatology [np-ES = 0.31]), cognition (Repeatable Battery for the Assessment of Neuropsychological Status Immediate Memory [np-ES = 0.25]), and general functioning (World Health Organization Disability Assessment Schedule [np-ES = 0.53]). Significantly greater than 50% of both groups correctly guessed their treatment assignment, indicating incomplete concealment of treatment allocation. CONCLUSIONS: This pilot RCT for ARHL and late-life depression was feasible to execute and showed clinical promise, but improved methods of blinding the experimental treatments are needed. Larger studies should investigate whether hearing remediation may be an effective preventative and/or therapeutic strategy for late-life depression and cognitive decline.

Expression patterns of programmed death-ligand 1 in esophageal adenocarcinomas: comparison between primary tumors and metastases.

Expression analysis of programmed death-ligand 1 (PD-L1) may be helpful in guiding clinical decisions for immune checkpoint inhibition therapy, but testing by immunohistochemistry may be hampered by heterogeneous staining patterns within tumors and expression changes during metastatic course. PD-L1 expression (clone SP142) was investigated in esophageal adenocarcinomas using tissue microarrays (TMA) from 112 primary resected tumors, preoperative biopsies and full slide sections from a subset of these cases (n = 24), corresponding lymph node (n = 55) and distant metastases (n = 17). PD-L1 expression was scored as 0.1-1, >1, >5, >50% positive membranous staining of tumor cells and any positive staining of tumor-associated inflammatory infiltrates and/or stroma cells. There was a significant correlation with overall PD-L1 expression between the full slide sections and the TMA (p = 0.001), but not with the corresponding biopsies. PD-L1 expression in tumor cells >1% was detected in 8.0% of cases (9/112) and 51.8% of cases (58/112) in tumor-associated inflammatory infiltrates and/or stroma cells of primary tumors. Epithelial expression in metastases was found in 5.6% of cases (4/72) and immune cell expression in 18.1% of cases (13/72), but did not correlate with the expression pattern in the primary tumor. Overall PD-L1 expression in the primary tumor did not influence survival. However, PD-L1 expression was correlated with the number of CD3+ tumor-infiltrating lymphocytes in the tumor center, and a combinational score of PD-L1 status/CD3+ tumor-infiltrating lymphocytes was correlated with patients' overall survival.

High intratumoural but not peritumoural inflammatory host response is associated with better prognosis in primary resected oesophageal adenocarcinomas.

The host inflammatory response plays an important role in many solid malignancies. Studies on oesophageal adenocarcinomas (EACs) point towards a beneficial role of pronounced immunoreaction, however, congruent results have yet to be obtained. We analysed 111 primary resected EAC using a tissue microarray containing three cores of the tumour centre and the periphery per case. Overall inflammation was assessed by histomorphology. Tumour infiltrating lymphocytes (TILs) were characterised by immunohistochemistry for CD3, CD8 and FoxP3, and evaluated by image analysis (Aperio ImageScope). High levels of inflammation in the tumour centre, but not the periphery were associated with better patient survival (p = 0.001), similar to high counts of intratumoural FoxP3+, CD3+, CD8+ TILs (p = 0.001; p = 0.027; p = 0.038) and a combination of CD3+/CD8+/FoxP3+ TILs, the latter displaying three different prognostic groups (triple high/mixed/triple low; p=0.003). Intratumoural inflammation [hazard ratio (HR) = 0.432; p = 0.030], FoxP3+ TIL counts (HR = 0.411; p = 0.033) and the combination CD3+/CD8+/FoxP3+ TILs (HR = 0.173; p = 0.006) were also independent prognostic parameters. In summary, both high grade total inflammation and high TIL counts in the tumour centre, but not the tumour periphery, show a beneficial prognostic impact on EAC. This may be a target for novel therapeutic options but also serves as prognostic indicator in these tumours.

Viral genomes in the pericardial fluid and in peri- and epicardial biopsies from a German cohort of patients with large to moderate pericardial effusions.

The aetiology of pericardial effusion has been generally assessed by clinical work-up only, which leaves a large cohort of patients with "idiopathic" effusions virtually undiagnosed. In accordance with the ESC guidelines, this contribution intends to change this attitude. After therapeutic or diagnostic pericardiocentesis of 259 patients with large to moderate pericardial effusions, pericardial fluid, epicardial and pericardial biopsies, and blood samples were analysed by PCR for cardiotropic microbial agents. Cytology, histology, immunohistology of tissue and fluids and laboratory tests were performed. Of the 259 patients, 35 % suffered from an autoreactive aetiology, 28 % suffered from a malignant and 14 % from an infectious cause. Investigating all samples by PCR, we identified viral genomes in 51 (19.7 %) patients, parvovirus B19 (B19 V) being identified in 25 and Epstein-Barr virus (EBV) in 19 cases. In patients with a sole infectious aetiology (n = 36), B19 V was detected in 21 and EBV in 10 cases. When differentiating with regard to the material investigated for the presence of cardiotropic viruses, parvovirus B19 was most often detected in the epicardium and EBV was most frequently detected in the pericardial fluid independent from the final diagnostic categorisation. Bacterial cultures including tests for tuberculosis were all negative. Molecular techniques improve sensitivity, specificity and diagnostic accuracy for the underlying aetiology in pericarditis patients with effusion. The identification of specific viral signatures will help to understand pathogenetic mechanisms in pericarditis and allow to tailor an adequate therapy beyond antiphlogistic treatment.

Alleviation of neuropathic pain hypersensitivity by inhibiting neuronal pentraxin 1 in the rostral ventromedial medulla.

Peripheral nerve injury causes spontaneous and long-lasting pain, hyperalgesia, and allodynia. Excitatory amino acid receptor-dependent increases in descending facilitatory drive from the brainstem rostral ventromedial medulla (RVM) contribute to injury-evoked hypersensitivity. Although increased excitability likely reflects changes in synaptic efficacy, the cellular mechanisms underlying injury-induced synaptic plasticity are poorly understood. Neuronal pentraxin 1 (NP1), a protein with exclusive CNS expression, is implicated in synaptogenesis and AMPA receptor recruitment to immature synapses. Its role in the adult brain and in descending pain facilitation is unknown. Here, we use the spared nerve injury (SNI) model in rodents to examine this issue. We show that SNI increases RVM NP1 expression and constitutive deletion or silencing NP1 in the RVM, before or after SNI, attenuates allodynia and hyperalgesia in rats. Selective rescue of RVM NP1 expression restores behavioral hypersensitivity of knock-out mice, demonstrating a key role of RVM NP1 in the pathogenesis of neuropathic pain.

The effect of dual tasks in locomotor path integration.

Without landmarks, navigation is based on information about self-velocity, which is transformed to position or orientation by a process called path integration. Simple path integration tasks, such as reaching a previously seen goal by blindfolded locomotion, were often considered to be automatic and not influenced by unrelated cognitive activity. However, we recently showed that reproduction of self-motion without landmark cues exhibits systematic dual-task interference. Since these experiments did not exclude that the dual task only interferes with memory for self-motion, we performed two additional experiments testing generic path integration. We show that locomotor homing and reaching predefined goals by active self-motion are affected systematically by a concurrent mental task. The similarity of the effects we found to those reported for duration estimation led us to the hypothesis that subjective time may be used as a temporal basis of path integration. Alternatively, path integration and duration estimation may be based on similar underlying neuronal mechanisms, for example, coincidence detection in neural oscillators.

Influence of uninformative visual cues on gravity perception.

The perception of the subjective direction of up (subjective visual zenith, SVZ) is influenced by various sensory cues, such as, vestibular and visual input, and by the idiotropic vector, which acts as prior information about self-orientation with respect to gravity. Here, we tested the influence of a subject-fixed visual cue, which was uninformative with respect to the direction of gravity, on SVZ settings in different pitch angles. Our results show that in most subjects the SVZ was influenced by the gravity-unrelated visual cue in a way suggesting that the cue's orientation was memorized in the first trial and used thereafter as reference.