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Introduction In a previous analysis of a case-control study of testicular cancer nested in a cohort of automobile workers, we observed an increased risk for testicular cancer among workers who had ever been involved in occupational metal-cutting tasks. We investigated whether this risk increase was due to exposure to metal-working fluids (MWF). Methods Occupational exposure to MWF was assessed in detail using a job-specific questionnaire for metal-cutting work. We calculated ORs and associated 95% CIs individually matched for age (±2 years) and adjusted for a history of cryptorchidism by conditional logistic regression. Results The prevalence of exposure to MWF was 39.8% among cases and 40.1% among controls. For total germ cell tumours and seminomas we did not observe risk increases for metal-cutting tasks or occupational exposure to MWF (OR 0.95; 95% CI 0.69 to 1.32 and OR 0.88; 95% CI 0.58 to 1.35, respectively). However, dermal exposure to oil-based MWF was associated with an increased risk for non-seminomatous testicular cancer. Dermal exposure to oil-based MWF for more than 5000 h showed particularly high risk estimates (OR 4.72; 95% CI 1.48 to 15.09). Discussion Long-term dermal exposure to oil-based MWF was a risk factor for the development of non-seminomatous testicular germ cell cancer. Possible measures to reduce exposure include the introduction of engineering control measures such as venting or enclosing of machines, and enforcing the use of personal protective equipment during metal cutting. [ABSTRACT FROM AUTHOR]

Abstract Aims To analyze the relationship between exposure to chlorinated and aromatic organic solvents and malignant lymphoma in a multi-centre, population-based case-control study. Methods Male and female patients with malignant lymphoma (n = 710) between 18 and 80 years of age were prospectively recruited in six study regions in Germany (Ludwigshafen/Upper Palatinate, Heidelberg/Rhine-Neckar-County, Würzburg/Lower Frankonia, Hamburg, Bielefeld/Gütersloh, and Munich). For each newly recruited lymphoma case, a gender, region and age-matched (± 1 year of birth) population control was drawn from the population registers. In a structured personal interview, we elicited a complete occupational history, including every occupational period that lasted at least one year. On the basis of job task-specific supplementary questionnaires, a trained occupational physician assessed the exposure to chlorinated hydrocarbons (trichloroethylene, tetrachloroethylene, dichloromethane, carbon tetrachloride) and aromatic hydrocarbons (benzene, toluene, xylene, styrene). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression analysis, adjusted for smoking (in pack years) and alcohol consumption. To increase the statistical power, patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis. Results We observed a statistically significant association between high exposure to chlorinated hydrocarbons and malignant lymphoma (Odds ratio = 2.1; 95% confidence interval 1.1–4.3). In the analysis of lymphoma subentities, a pronounced risk elevation was found for follicular lymphoma and marginal zone lymphoma. When specific substances were considered, the association between trichloroethylene and malignant lymphoma was of borderline statistical significance. Aromatic hydrocarbons were not significantly associated with the lymphoma diagnosis. Conclusion In accordance with the literature, this data point to a potential etiologic role of chlorinated hydrocarbons (particularly trichloroethylene) and malignant lymphoma. Chlorinated hydrocarbons might affect specific lymphoma subentities differentially. Our study does not support a strong association between aromatic hydrocarbons (benzene, toluene, xylene, or styrene) and the diagnosis of a malignant lymphoma.

Background and Objectives : Although left ventricular excessive trabeculation (LVET) can cause heart failure, arrhythmia and thromboembolism, limited literature is available on the ECG characteristics of primary LVET with preserved left ventricular function (EF). We aimed to compare the ECG characteristics and cardiac MR (CMR) parameters of LVET individuals with preserved left ventricular EF to a control (C) group, to identify sex-specific differences, and to compare the genetic subgroups of LVET with each other and with a C population. Methods : In our study, we selected 69 LVET individuals (EF > 50%) without any comorbidities and compared them to 69 sex- and age-matched control subjects (42% females in both groups, p = 1.000; mean age LVET-vs-C: 38 ± 14 vs. 38 ± 14 years p = 0.814). We analyzed the pattern and notable parameters of the 12-lead ECG recordings. We determined the volumetric and functional parameters, as well as the muscle mass values of the left and right ventricles (LV, RV) based on the CMR recordings. Based on the genotype, three subgroups were established: pathogenic, variant of uncertain significance and benign. Results : In the LVET group, we found normal but elevated volumetric and muscle mass values and a decreased LV_EF, wider QRS, prolonged QTc, higher RV Sokolow index values and lower T wave amplitude compared to the C. When comparing MR and ECG parameters between genetic subgroups, only the QTc showed a significant difference. Over one-third of the LVET population had arrhythmic episodes and a positive family history. Conclusions : The subclinical morphological and ECG changes and the clinical background of the LVET group indicate the need for follow-up of this population, even with preserved EF.

Road mortality can be a serious threat to different animals, including snakes. However, mortality patterns can vary between species, intraspecific groups, locations and time. We compared the number of road-killed individuals (carcasses) of two semiaquatic water snakes ( Natrix natrix and N. tessellata ) on 58 km of road sections bordered by an active floodplain and a flood-protected former floodplain on one side and mountainous areas on the other in NE Hungary based on surveys conducted once every two weeks in three non-consecutive years. The results showed high road mortality of snakes, with a spring and an autumn peak corresponding to the times when snakes emerge from and return to hibernating sites. The results show that small-scale spatial differences in road mortality were mediated by landscape structure along the road, while the effects of traffic volume, flood regime and the age and sex of the individuals were negligible. For conservation, the study suggests that establishing culvert passages under the road and/or artificial hibernating sites on the floodplain-side of the roads in critical sections can be promising in reducing road-related mortality., Competing Interests: The authors declare there are no competing interests., (©2024 Szabolcs et al.)

Background: Cardiac rotational parameters in primary symptomatic left ventricular noncompaction (LVNC) with preserved left ventricular ejection fraction (LVEF) are not well understood. We aimed to analyze cardiac rotation measured with cardiac magnetic resonance feature-tracking (CMR-FT) and speckle-tracking echocardiography (Echo-ST) in LVNC morphology subjects with preserved LVEF and different genotypes and healthy controls., Methods: Our retrospective study included 54 LVNC subjects with preserved LVEF and 54 control individuals. We evaluated functional and rotational parameters with CMR in the total study population and with echocardiography in 39 LVNC and 40 C individuals. All LVNC subjects were genotyped with a 174-gene next-generation sequencing panel and grouped into the subgroups: benign (B), variant of uncertain significance (VUS), and pathogenic (P)., Results: In comparison with controls, LVNC subjects had reduced apical rotational degree (p = 0.004) and one-third had negative apical rotation. While the degree of apical rotation was comparable between the three genetic subgroups, they differed significantly in the direction of apical rotation (p<0.001). In contrast to control and B groups, all four studied cardiac rotational patterns were identified in the P and VUS subgroups, namely normal rotation, positive and negative rigid body rotation, and reverse rotation. When the CMR-FT and Echo-ST methods were compared, the direction and pattern of cardiac rotation had moderate to good association (p<0.001) whereas the rotational degrees showed no reasonable correlation or agreement., Conclusion: While measuring cardiac rotation using both CMR-FT and Echo-ST methods, subclinical mechanical differences were identified in subjects with LVNC phenotype and preserved LVEF, especially in cases with genetic involvement., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Grebur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Seriously injured persons with pre-existing psychiatric conditions or those injured due to violent crimes represent a particularly vulnerable treatment group., Methods: All patients with injuries from suicidal attempts (PSAs) or patients with injuries from violent offenses (PVOs) that presented to the university emergency room of a Level 1 trauma center in Germany between 1 January 2017 and 31 November 2022 were retrospectively investigated., Results: It can be seen that PVOs were significantly younger compared to PSAs ( p = 0.03). Total hospital stay was significantly longer for PSAs compared to PVOs ( p < 0.001). PSAs were also significantly more severely injured than PVOs ( p < 0.001). Our study was able to show a significant difference between both patient groups in the region of injury ( p < 0.001). PSAs had a significantly more extensive psychiatric history than PVOs ( p < 0.001)., Conclusion: Injuries from suicide attempts and violent offenses are a serious and growing public health problem, but one that can be addressed through timely, evidence-based, and often cost-effective interventions. It requires early interaction among multiple disciplines and a standardized approach.

Introduction: The genotype of symptomatic left ventricular noncompaction phenotype (LVNC) subjects with preserved left ventricular ejection fraction (LVEF) and its effect on clinical presentation are less well studied. We aimed to characterize the genetic, cardiac magnetic resonance (CMR) and clinical background, and genotype-phenotype relationship in LVNC with preserved LVEF., Methods: We included 54 symptomatic LVNC individuals (LVEF: 65 ± 5%) whose samples were analyzed with a 174-gene next-generation sequencing panel and 54 control (C) subjects. The results were evaluated using the criteria of the American College of Medical Genetics and Genomics. Medical data suggesting a higher risk of cardiovascular complications were considered "red flags"., Results: Of the LVNC population, 24% carried pathogenic or likely pathogenic (P) mutations; 56% carried variants of uncertain significance (VUS); and 20% were free from cardiomyopathy-related mutations. Regarding the CMR parameters, the LVNC and C groups differed significantly, while the three genetic subgroups were comparable. We found a significant relationship between red flags and genotype; furthermore, the number of red flags in a single subject differed significantly among the genetic subgroups ( p  = 0.002) and correlated with the genotype ( r  = 0.457, p  = 0.01). In 6 out of 7 LVNC subjects diagnosed in childhood, P or VUS mutations were found., Discussion: The large number of P mutations and the association between red flags and genotype underline the importance of genetic-assisted risk stratification in symptomatic LVNC with preserved LVEF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Grebur, Mester, Fekete, Kiss, Gregor, Horváth, Farkas-Sütő, Csonka, Bödör, Merkely, Vago and Szűcs.)

Introduction: Combined PCL injuries involving the posteromedial/-lateral corner (PMC/PLC) usually require surgical management. Literature shows controversy regarding the standards of treatment. Suture-augmented repair leads to excellent results in acute knee dislocations but has not been investigated clinically in combined PCL injuries. The purpose of this multicentre study was to evaluate the clinical outcome of this technique in acute combined PCL injuries., Materials & Methods: N = 33 patients with acute combined PCL injuries involving the PMC/PLC were treated by one-stage suture repair with ligament bracing of the PCL and suture repair of the accompanying PMC/PLC injuries with/without ligament bracing or primary augmentation by semitendinosus autograft. Outcome was assessed by IKDC questionnaire, Lysholm Score, Tegner Activity Scale and KOOS. Additional PCL stress-radiography was performed., Results: N = 31 patients with combined PCL injuries (female: male = 7:24; age 39.1 ± 13.8 years) with a follow-up of 16.8 ± 9.6 months were finally evaluated. 18 had PMC injuries, 13 PLC injuries. 32.2% presented with accompanying meniscal tears (70% medial meniscus). 19.4% showed cartilage injuries grade III-IV. Complications included one infection and four knee stiffnesses. Three had symptomatic postoperative instability, all affiliated to the PLC group. The IKDC was 69.8 ± 16.5, Lysholm score 85 ± 14.4 and KOOS 89.7 ± 8.1. Median loss of activity (Tegner) was 0.89 ± 1.31. Comparing PMC and PLC, all scores showed a tendency towards more favourable outcomes in the PMC group (n.s.). Stress-radiography showed an overall side-to-side difference of 3.7 ± 3.8 mm. Subgroup evaluation showed statistically significant better results (p = 0.035) of PMC (2.5 ± 1.5 mm) versus PLC (5.8 ± 5.6 mm)., Conclusions: One-stage suture repair with ligament bracing is a viable technique for acute combined PCL injuries and predominantly leads to good and excellent clinical outcomes. Patients with PLC injuries show a tendency towards inferior outcomes and higher instability rates compared to PMC injuries. These results may help in therapy planning and counselling patients with these rare injury pattern., Level of Evidence: Level II., (© 2023. The Author(s).)

Highlights of right ventricular characteristics of left ventricular noncompaction using 3D echocardiography. The aspects of right ventricular volumes and function investigated with 3D echocardiography in a large cohort of left ventricular noncompaction morphology (LVNC) population remains unclear. The objective of our research was to study the left (LV) and right (RV) ventricular parameters using 3D echocardiography and analyze the clinical features of a LVNC population with preserved LV ejection fraction (EF > 50 %) in comparison with healthy controls (HC). We selected 41 LVNC subjects with preserved LV function (EF: 52.91 ± 3 %, male n = 26) and without any comorbidities and compared them with an age and sex-matched HC. Three dimensional endocardial contours were evaluated to determine the following LV and RV parameters: end-diastolic (EDV) and end-systolic (ESV) volumes, stroke volume, EF, LV global longitudinal and circumferential strain and RV septal and free wall longitudinal strain. Regarding the clinical characteristics, the family involvement had a notable proportion, accounting for 51%. The EF and strain values of the LVNC population were significantly decreased in both RV and LV compared to HC. Although the LV volumes of the LVNC group were significantly elevated, the RV volumetric parameters did not differ significantly compared to controls. We found significant correlations between LV and RV volumetric and functional parameters and linear regression models showed that LV EDV and LV ESV determined the RV volumetric values. While the alteration and relationship of the RV parameters may represent the potential of biventricular involvement, clinical characteristics of the LVNC group underlines the necessity of monitoring this population, even with preserved EF., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Published by Elsevier B.V.)

Introduction: Posttraumatic MRI of ACL tears show a high prevalence of bone bruise (BB) without macroscopic proof of chondral damage. Controversial results are described concerning the association between BB and outcome after ACL tear. Aim of this study is to evaluate the influence of distribution, severity and volume of BB in isolated ACL injuries on function, quality of life and muscle strength following ACL reconstruction (ACLR)., Materials and Methods: MRI of n = 122 patients treated by ACLR without concomitant pathologies were evaluated. BB was differentiated by four localizations: medial/lateral femoral condyle (MFC/LFC) and medial/lateral tibial plateau (MTP/LTP). Severity was graded according to Costa-Paz. BB volumes of n = 46 patients were quantified (software-assisted volumetry). Outcome was measured by Lysholm Score (LS), Tegner Activity Scale (TAS), IKDC, isokinetics and SF-36. Measurements were conducted preoperatively (t0), 6 weeks (t1), 26 weeks (t2) and 52 weeks (t3) after ACLR., Results: The prevalence of BB was 91.8%. LTP was present in 91.8%, LFC 64.8%, MTP 49.2% and MFC 28.7%. 18.9% were classified Costa-Paz I, 58.2% II and 14.8% III. Total BB volume was 21.84 ± 15.27 cm 3 , the highest value for LTP (14.31 ± 9.93 cm 3 ). LS/TAS/IKDC/SF-36/isokinetics improved significantly between t0-t3 (p < 0.001). Distribution, severity and volume had no influence on LS/TAS/IKDC/SF-36/isokinetics (n.s.)., Conclusions: No impact of BB after ACLR on function, quality of life and objective muscle strength was shown, unaffected by concomitant pathologies. Previous data regarding prevalence and distribution is confirmed. These results help surgeons counselling patients regarding the interpretation of extensive BB findings. Long-time follow-up studies are mandatory to evaluate an impact of BB on knee function due to secondary arthritis., (© 2023. The Author(s).)

As survival rates associated with the multimodal treatment of malignant bone cancer (osteosarcoma and Ewing's sarcoma) are satisfactory, health-related quality of life and the return to activity and sports by the affected patients have attracted increasing attention in recent years. Nowadays, limbs can be salvaged for most patients using modular endoprostheses. Such patients are typically adolescents and young adults who have high activity levels and thereby high demands for multimodal cancer treatment. This study aimed to evaluate the activity levels and sporting proficiencies that can be attained after modular endoprosthetic treatment of bone sarcomas as well as the extent to which physiotherapeutic and sports interventions influence functional outcome and activity levels.This non-systematic review of the literature focused on the return to activity and sports after modular endoprosthetic treatment of lower extremities bone sarcomas in adolescents and young adults. The electronic database PubMed was screened for relevant publications on this issue. A treatment algorithm for return to activity and sports in tumor orthopaedics is proposed.The objective activity level (gait cycles per day and gait intensities) in patients treated for bone sarcomas is reduced in short- and long-term follow-ups compared with healthy controls and patients with other cancers (leukaemia). Although a negative impact is observed in terms of motor performance, it shows improvement over time. Functional assessment at 12 postoperative months is sensible as neoadjuvant chemotherapy is completed by then. In long-term follow-up, patients with bone sarcomas can achieve high sports activity levels, i.e., type of sport, frequency/week and UCLA score, after modular endoprosthetic reconstruction. The maximum level is attained at 5 years postoperatively. Nevertheless, there is a shift from high- and intermediate- to low-impact sports. Only 20% of the patients participate in school sports regularly without limitations. The localisation of bone sarcoma, but not the rate of postoperative complications, influences the postoperative activity level. Individualised sports-related interventions during and after multimodal treatment can improve the short-term activity levels; moreover, "serious games" can improve motor performance and postural control. There is no evidence that intense activity levels leads to early loosening of the endoprosthesis. There is insufficient valid data on activity and sports after modular endoprosthetic treatment of bone sarcomas of the upper extremities.High preoperative activity levels of young patients with bone sarcomas must be considered in tumour orthopaedics. Limitations on sports activities have a significant negative impact on the quality of life and mental health of such patients. Therefore, tumour orthopaedic treatment has to focus on preserving an improvement in these factors. The overall existing evidence concerning this issue is weak. Additional studies to evaluate the ability to return to specific sports activities are desirable, as well as prospective interventional studies., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

We present a new open source dataset FLODIS that links estimates of flood-induced human displacements, fatalities, and economic damages to flooded areas observed through remote sensing. The dataset connects displacement data from the Internal Displacement Monitoring Centre (IDMC), as well as data on fatalities and damages from the Emergency Events Database (EM-DAT), with the Global Flood Database (GFD), a satellite-based inventory of historic flood footprints. It thereby provides a spatially explicit estimate of the flood hazard underlying each individual disaster event. FLODIS contains two datasets with event-specific information for 335 human displacement events and 695 mortality/damage events that occurred around the world between 2000 and 2018. Additionally, we provide estimates of affected population, GDP, and critical infrastructure, as well as socio-economic indicators; and we provide geocoding for displacement events ascribed to other types of disasters, such as tropical cyclones, so that they may be linked to corresponding hazard estimates in future work. FLODIS facilitates integrated flood risk analysis, allowing, for example, for detailed assessments of local flood-damage and displacement vulnerability., (© 2023. The Author(s).)

Aim: We have previously reported that polyfunctional T cell responses can be induced to the cancer testis antigen NY-ESO-1 in melanoma patients injected with mature autologous monocyte-derived dendritic cells (DCs) loaded with long NY-ESO-1-derived peptides together with α-galactosylceramide (α-GalCer), an agonist for type 1 Natural Killer T (NKT) cells., Objective: To assess whether inclusion of α-GalCer in autologous NY-ESO-1 long peptide-pulsed DC vaccines (DCV + α-GalCer) improves T cell responses when compared to peptide-pulsed DC vaccines without α-GalCer (DCV)., Design, Setting and Participants: Single-centre blinded randomised controlled trial in patients ≥ 18 years old with histologically confirmed, fully resected stage II-IV malignant cutaneous melanoma, conducted between July 2015 and June 2018 at the Wellington Blood and Cancer Centre of the Capital and Coast District Health Board., Interventions: Stage I. Patients were randomised to two cycles of DCV or DCV + α-GalCer (intravenous dose of 10 × 10 6 cells, interval of 28 days). Stage II. Patients assigned to DCV + α-GalCer were randomised to two further cycles of DCV + α-GalCer or observation, while patients initially assigned to DCV crossed over to two cycles of DCV + α-GalCer., Outcome Measures: Primary: Area under the curve (AUC) of mean NY-ESO-1-specific T cell count detected by ex vivo IFN-γ ELISpot in pre- and post-treatment blood samples, compared between treatment arms at Stage I. Secondary: Proportion of responders in each arm at Stage I; NKT cell count in each arm at Stage I; serum cytokine levels at Stage I; adverse events Stage I; T cell count for DCV + α-GalCer versus observation at Stage II, T cell count before versus after cross-over., Results: Thirty-eight patients gave written informed consent; 5 were excluded before randomisation due to progressive disease or incomplete leukapheresis, 17 were assigned to DCV, and 16 to DCV + α-GalCer. The vaccines were well tolerated and associated with increases in mean total T cell count, predominantly CD4 + T cells, but the difference between the treatment arms was not statistically significant (difference - 6.85, 95% confidence interval, - 21.65 to 7.92; P = 0.36). No significant improvements in T cell response were associated with DCV + α-GalCer with increased dosing, or in the cross-over. However, the NKT cell response to α-GalCer-loaded vaccines was limited compared to previous studies, with mean circulating NKT cell levels not significantly increased in the DCV + α-GalCer arm and no significant differences in cytokine response between the treatment arms., Conclusions: A high population coverage of NY-ESO-1-specific T cell responses was achieved with a good safety profile, but we failed to demonstrate that loading with α-GalCer provided an additional advantage to the T cell response with this cellular vaccine design., Clinical Trial Registration: ACTRN12612001101875. Funded by the Health Research Council of New Zealand., (© 2023. The Author(s).)

Background: The quantitative differences of left and right ventricular (LV, RV) parameters of using different cardiac MRI (CMR) post-processing techniques and their clinical impact are less studied. We aimed to assess the differences and their clinical impact between the conventional contouring (CC) and the threshold-based (TB) methods using 70% and 50% thresholds in different hypertrabeculated conditions., Methods: This retrospective study included 30 dilated cardiomyopathy, 30 left ventricular non-compaction (LVNC), 30 arrhythmogenic cardiomyopathy patients, 30 healthy athletes and 30 healthy volunteers. All participants underwent CMR imaging on 1.5 T. Cine sequences were used to derive measures of the cardiac volumes, function, total muscle mass (TMi) and trabeculae and papillary muscle mass (TPMi) using CC and TB segmentation methods., Results: Comparing the CC and the 70% and 50% threshold TB methods, the LV and RV volumes were significantly lower, the ejection fraction (EF) and the TMi were significantly higher with the TB methods. Between the two threshold setups, only TPMi was significantly higher with the 70% threshold. Regarding the clinical benefits, the LVNC was the only group in whom all the diagnostic and therapeutic decisions and risk stratification were influenced using the TB method. Diagnostic changes occurred in three-quarters of the population, and all the cardiomyopathy groups were affected regarding the decision-making about pharmaco- and device therapy., Conclusions: Using the TB method, only TPMi was significantly higher with the 70% threshold than the 50% setup, and both of them differed significantly from the CC technique, with relevant clinical impacts in all patient groups., Competing Interests: Declaration of Competing Interest The authors have no conflict of interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The cortical desmoid (DFCI) of the posteromedial femoral condyle is considered an asymptomatic incidental finding in adolescents without clinical relevance. The aim of this study was to evaluate the clinical relevance of DFCI from both a tumor orthopedic and sports medicine point of view., Methods: n = 23 patients (13.74 ± 2.74 years; nineteen female, four male) with DFCI of the posteromedial femoral condyle were included. A localized posteromedial knee pain on exertion was differentiated from non-specific knee pain. Symptom duration, additional pathologies, number of MRIs, sports activity and training intensity, downtime, therapeutic modalities, and relief/remission of symptoms were documented. The Tegner activity scale (TAS) and Lysholm score (LS) were collected. The influence of specific posteromedial pain, MRI presence of paratendinous cysts, sports level as well as physiotherapy on downtime and LS/TAS was statistically analyzed., Results: 100% reported knee symptoms at initial presentation. A localized posteromedial pain was documented in 52%. In 16/23 (70%) additional functional pathologies were diagnosed. Patients were physically highly active with high training intensities (6.52 ± 5.87 h/week) and performance level (65% competitive vs. 35% recreational). Patients underwent 1.91 ± 0.97 MRIs (max four). Symptom duration was 10.48 ± 11.02 weeks. A follow-up examination was performed after 12.62 ± 10.41 months ( n = two lost to follow-up). 17/21 had physiotherapy, on average 17.06 ± 13.33 units. Overall downtime was 13.39 ± 12.50 weeks, the return-to-sports (RTS) rate 81%. 100%/38% reported a relief/remission of complaints. LS was 93.29 ± 7.95, median TAS before onset of knee complaints/at follow-up 7 (6-7)/7 (5-7). Specific posteromedial pain, presence of paratendinous cysts, sports level and physiotherapy had no significant influence on downtime and outcome parameters (n.s.)., Conclusions: DFCI as a pathognomonic finding is recurrently encountered in the MRIs of children and adolescents. This knowledge is essential to spare patients from overtreatment. Contrary to the literature, the present results implicate a clinical relevance of DFCI particularly in those who are physically highly active with localized pain on exertion. Structured physiotherapy as basic treatment is recommended.

Background: The actual number of accidents in e‑scooter drivers in Germany seems to be significantly higher than the current figures from the Statistisches Bundesamt suggest. This epidemiological study examines e‑scooter injuries and compares them with e‑bike and bicycle injuries., Objective: In order to create a comparable database on the dangers of e‑scooters, e‑bikes and bicycles, the typical injury patterns were analyzed and prevention options derived from them., Material and Methods: All accidents involving e‑scooters, e‑bikes and bicycles that were presented via the university emergency room of a level 1 trauma center between 15 June 2019 and 31 October 2020 were prospectively investigated., Results: In our study, 68 accidents in e‑scooter drivers were included, of which only 11.8% (n = 8) were recorded by the police. Significantly more of them were male than female (p = 0.032) with a mean age of 31.1 (±13) years. At the same time, we registered 34 accidents in e‑bike riders and 356 in cyclists. In all three groups, most injuries occurred to the head, followed by injuries to the upper extremities. Significantly more e‑scooter drivers had an ISS ≥ 16 than in the group of injured cyclists (p = 0.016). E‑scooter riders who had an accident had a significantly longer length of stay in hospital, than e‑bike riders (p = 0.003) and cyclists (p = 0.001), 52.9% (n = 18) of e‑bike riders and 53.3% (n = 113) cyclists wore a helmet, compared to only 1.5% (n = 1) of e‑scooter riders. The most common cause of accidents among e‑bike riders (17.7%; n = 6) and cyclists (10.4%; n = 37) was slipping away on tram rails, while for e‑scooter riders it was colliding with a curb (7.4%; n = 5)., Conclusion: The three patient collectives examined showed different causes and profiles of injuries. The reasons for an increased proportion of seriously injured people compared to cyclists are electromobility, driving under the influence of alcohol and inadequate wearing of a helmet on e‑scooters when head injuries dominate. 73.5% (n = 50) of the e‑scooter accidents recorded by us were not registered by the police and therefore do not appear in the current statistics of the statistisches Bundesamt. As a result, a much higher number of e‑scooter accidents can be assumed. Preventive measures could include the introduction of compulsory helmets, a higher number of traffic controls and the expansion of bike tracks., (© 2022. The Author(s).)

(1) Background: The treatment of proximal humeral fractures (PHFs) is debated controversially. Current clinical knowledge is mainly based on small single-center cohorts. The goal of this study was to evaluate the predictability of risk factors for complications after the treatment of a PHF in a large clinical cohort in a multicentric setting. (2) Methods: Clinical data of 4019 patients with PHFs were retrospectively collected from 9 participating hospitals. Risk factors for local complications of the affected shoulder were assessed using bi- and multivariate analyses. (3) Results: Fracture complexity with n = 3 or more fragments, cigarette smoking, age over 65 years, and female sex were identified as predictable individual risk factors for local complications after surgical therapy as well as the combination of female sex and smoking and the combination of age 65 years or older and ASA class 2 or higher. (4) Conclusion: Humeral head preserving reconstructive surgical therapy should critically be evaluated for patients with the risk factors abovementioned.

Background: Organization of mass sport events in the COVID-19 era is utterly complicated. Containments measures, required to avoid a virus outbreak, force athletes to compete under circumstances they never experienced before, most likely having a deleterious effect on their performance., Purpose: We aimed to design a so-called athlete-friendly bubble system for the International Swimming League 2020 event, which is strict enough to avoid a COVID-19 outbreak, but still provides a supportive environment for the athletes., Methods: To avoid the feeling of imprisonment, athletes were permitted to spend a certain amount of time in the parks surrounding the hotels. Such alleviations were possible to apply with strict adherence to the hygienic and social distancing protocols and regular COVID-19 testing. Evaluation of every COVID-19 positive case was key, and if prolonged PCR positivity or false positive PCR result was identified, the unnecessary quarantine was planned to be lifted. Return to play protocol (RTP) was planned, in case of a COVID-19 infection of an athlete inside the bubble. To test, if the athlete-friendly system provided a supportive environment, we evaluated athlete performance., Results: 11,480 PCR tests were performed for 1,421 individuals. 63 COVID-19 positive cases were detected, of which 5 turned out to be clinically insignificant, either because of prolonged PCR positivity or because of a false positive result. 93.1% of the positive cases were detected in the local crew, while no athlete got infected inside the bubble, as the two infected athletes were tested positive upon arrival. RTP was provided for two athletes. 85% of the athletes showed improvement during the bubble and 8 world records were broken., Conclusion: The applied protocol proved to be effective, as no athlete got infected inside the bubble, moreover, the athlete-friendly system supported the athletes to improve their performance.

Introduction: A rupture of the pectoralis major muscle is a rare injury pattern overall, but it is frequently described in athletes, particularly in weightlifting. The risk of sustaining this type of injury is present especially during the eccentric phase of muscle loading. An association between such injuries and the abuse of anabolic steroids is described in the literature, but there is no coherent evidence to support this. We report the case of a young patient with a normal habitus who suffered a humeral rupture of the pectoralis major muscle during recreational sports. There was no history of excessive weight training or use of anabolic steroids., Case History: This 33-year-old patient reported a sudden onset of left pectoral pain during training on the chest fly machine as well as a whip-like popping sound, followed by an immediate painful restriction of movement in the left arm. A clinical examination revealed a mild haematoma located on the left medial upper arm with localised tenderness and a discrete asymmetry of the contour of the pectoral muscles. Due to the typical medical history, we established the indication for surgical exploration although the clinical picture was rather discrete and only an incomplete rupture was seen in an MRI scan. Intraoperatively, we detected a complete rupture of the sternocostal part of the pectoralis major muscle with marked retraction and haematoma. Reinforcement and reinsertion were performed at the "footprint" using titanium anchors (2 x 5.5mm Corkscrew FT, Arthrex, Florida). The patient was able to resume his sports activities at the pre-traumatic level four months after surgery., Conclusion: A rupture of the insertion of the pectoralis major muscle must also be considered in amateur athletes with a typical history. The characteristic clinical symptoms described in the literature mostly refer to competitive athletes and bodybuilders, but these injuries can also be diagnosed in amateur athletes with lower muscle mass by subtle clinical examination. Nevertheless, there is a considerable risk of underestimating the extent of the injury. In case of doubt, surgical exploration should be performed promptly in amateur athletes. Surgical refixation of the humeral rupture of the pectoralis major muscle is the gold standard and should not be reserved to high-performance athletes., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

This retrospective cross-sectional epidemiological study deals with sport-specific injury patterns in show jumping. A total of 363 show jumpers of all levels (S) answered a retrospective questionnaire about injuries and overuse damages which occurred in the course of their careers. Demographic data and information on injuries in various body regions were collected. In addition to descriptive analysis, significance tests were performed. For better statistical comparability with other sports, exposure time was extrapolated with total career duration and weekly training hours, and injuries per 1000 jumping hours were calculated. The study included 251 (69%) women and 112 (31%) men, who were on average 26.9 ± 10.9 years old. The injury rate for the entire collective was 3.7 per 1000 h of exposure. The most frequently affected body region was the head (31%). Overuse complaints play a subordinate role and mainly affect the upper extremities (65%). The riders of the professional lower performance levels are less likely to injure themselves per 1000 h than riders of the higher performance levels. Riders who often or always wore a helmet suffered significantly fewer head injuries ( p = 0.008) and had a significantly lower total injury duration than riders who did not wear a helmet ( p = 0.006). Similarly, the study showed that riders who often or always wore a safety vest suffered significantly fewer spinal injuries ( p = 0.017) and had significantly fewer injuries per 1000 riding hours ( p = 0.031) than riders who did not wear a safety vest. Based on the present results, there should be an extension of the general helmet requirement and a requirement to wear safety vests in show jumping in general.

Competing Interests: Martin Glombitza declares that he signed a consultant contract with BonAlive in May 2017.

Background: Locking plate osteosynthesis via an L-shaped lateral approach is the gold standard in treating displaced intra-articular calcaneal fractures. High complication rates are known for this approach. The most frequent complications are wound edge necrosis and superficial wound infections. To reduce complication rates, a locking intramedullary nail (C-Nail) was developed that can be implanted minimally invasively via a sinus tarsi approach. We compared the postoperative complication rate and the outcome of plate osteosynthesis versus C-Nail in displaced intra-articular calcaneal fractures., Methods: All patients with calcaneal fractures who received osteosynthesis with either plate or C-Nail between January 2016 and October 2019 in our institution were retrospectively analyzed. A subgroup analysis was performed with matched pairs (matching Sanders type, age, Böhler's angle postoperative in normal range, 33 pairs). Endpoints were postoperative complication rate, bone healing, full weight-bearing and functional outcome. Treatment groups were compared using Fisher's exact test for binary data, and Mann-Whitney U-test for continuous data. A p-value < 0.05 was considered statistically significant., Results: One hundred and one calcaneal fractures were included (C-Nail n = 52, plate n = 49). Patients with C-Nail developed significantly less postoperative complications (p = 0.008), especially wound edge necrosis (p < 0.001). Screw malposition was found more often in the C-Nail group. The rates of achieving full weight-bearing as well as bone healing were comparable in both groups, but in each case significant faster in the C-nail subgroup. The results of the matched-pairs analysis were comparable., Conclusions: The postoperative complication rate was significantly lower in the C-Nail group. The C-Nail appears to be a successful alternative in the treatment of calcaneal fractures, even in Sanders IV fractures because of the minimal-invasive implantation as well as the high primary stability. Long-term analysis of this new implant including elaboration on functional outcome is planned., Trial Registration: Deutsches Register Klinischer Studien (DRKS) DRKS00020395 . Date of registration 3 January 2020.

Introduction : The goals of osteomyelitis therapy are successful control of infection and reconstruction of the bone. The gold standard for filling defects is the autologous bone graft. Bioactive glass S53P4 is an inorganic bone substitute. We compared the outcome of using bioactive glass (BAG) versus autologous bone graft (AB) in patients with infected non-union. Methods : Patients with chronic osteomyelitis and infected non-union who received either bioactive glass or autologous bone grafts between 2013 and 2017 were analyzed retrospectively. The primary endpoint was successful control of infection during follow-up. Secondary endpoints were bone healing, functional outcome, and occurrence of complications. Results : Eighty-three patients were analyzed (BAG n = 51 , AB n = 32 ). Twenty-one patients experienced reinfection (BAG n = 15 , 29 %; AB n = 6 , 19 %). Seventy-eight patients achieved full weight bearing (BAG n = 47 , 92 %; AB n = 31 , 97 %). Sixty-four patients had complete bone healing at the end of the follow-up period (BAG n = 39 , 77 %; AB n = 25 , 78 %). There were no significant differences between the groups with respect to the primary or secondary endpoints. Patients with multidrug-resistant pathogens had a significantly higher rate of incomplete bone healing ( p = 0 .033) and a 3-fold higher risk of complications in both groups. Conclusions : Bioactive glass appears to be a suitable bone substitute not only for successful control of infection and defect filling but also for bone healing in cases of infected non-union. In our study, bioactive glass was neither superior nor inferior to autologous bone graft with regard to the primary and secondary endpoints. Further studies with larger numbers of patients are required., Competing Interests: The authors declare that they have no conflict of interest., (Copyright: © 2021 Eva Steinhausen et al.)

In Germany, Inline Skater Hockey (ISH) is played by about 7500 active players on inline skates with equipment comparable to ice hockey using a hard-plastic ball. The aim of this retrospective epidemiological cross-sectional study is to record the frequency and types of injuries in this sport, for which there is a lack of medically adequate studies in the literature. A questionnaire comprising 112 items was used to collect demographic data, injuries in eight body regions and defined overuse injuries. 274 ISH players with an average age of 24.5 ± 6.2 years and an exposure time of 2787 ± 2063 hours were examined. 5701 injuries were recorded, 60.5 % of which were minor bruises, abrasions and wounds. The total injury rate per 1000 hours was 9.6 ± 17.7, with an injury-related break of 12.8 ± 21.8 weeks per player. Field players with visors had highly significantly fewer head injuries (2.8 ± 6.1 vs. 8.9 ± 13.1; p < 0.001) with highly significantly (p < 0.001) fewer lacerations, nasal bone fractures, eye injuries and dental injuries. There was a weak negative correlation between facial protection and number of head injuries (r = -0.386, p < 0.001). In conclusion, frequency and types of injuries in ISH are comparable to ice hockey during training. In accordance with ice hockey, protective equipment in ISH can significantly reduce the occurrence of head injuries. Preventive attention should be paid to the wearing of a full visor and to education about the occurrence of concussions despite the use of a protective helmet., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Background: Coagulopathy following severe trauma contributes significantly to mortality. Impaired clotting factors have been observed in adult trauma patients, but in pediatric trauma victims their activity has not yet been investigated., Methods: Sixteen pediatric trauma patients were evaluated according to the ISS and assigned to two cohorts. An additional control group (CO; n = 10) was formed. Routine coagulation parameters and the soluble clotting factors (F) were tested. Nonparametric data was analyzed using the Mann-Whitney U test. Results are reported as median and interquartile range., Results: The ISS of severely (SI, n = 8) and mildly (MI, n = 8) injured children differed significantly (25 [19-28] vs. 5 [4-6]; p < 0.001). INR was elevated in the SI cohort only when compared to the CO (1.21 [1.04-1.58] vs. 0.96 [0.93-1.00]; p = 0.001). Differences between SI and MI were found for FII (67 [53-90] vs. 82 [76-114] %; p = 0.028), FV (76 [47-88] vs. 92 [82-99] %; p = 0.028), and FXIII (67 [62-87] vs. 90 [77-102] %; p = 0.021). Comparison of the SI with the CO (FII 122 [112-144] %; p < 0.001; FV 123 [100-142] %; p = 0.002; and FXIII 102 [79-115] %; p = 0.006) also revealed a reduction in the activity of these factors. Furthermore, fibrinogen (198 [80-242] vs. 296 [204-324] mg/dl; p = 0.034), FVII (71 [63-97] vs. 114 [100-152] %; p = 0.009), FIX (84 [67-103] vs. 110 [90-114] %; p = 0.043), and FX (70 [61-85] vs. 122 [96-140] %; p = 0.001) were reduced in the SI in comparison with the CO. Finally, FVIII was considerably, yet not significantly, increased in both patient cohorts (235 [91-320] % and 197 [164-238] %, respectively)., Conclusions: This study proves that children suffer a depletion of clotting factors following severe injury which basically reflects the findings for adult trauma patients. Attempts to correct the impaired clotting factor activity could be based on a specific hemostatic therapy involving administration of coagulation factors. Nevertheless, therapeutic implications need to be investigated in future studies.

Introduction: Autologous T-cells transduced to express a chimeric antigen receptor (CAR) directed against CD19 elicit high response rates in relapsed or refractory (r/r) B-cell non-Hodgkin lymphoma (B-NHL). However, r/r B-NHL remissions are durable in fewer than half of recipients of second-generation CAR T-cells. Third-generation (3G) CARs employ two costimulatory domains, resulting in improved CAR T-cell efficacy in vitro and in animal models in vivo. This investigator-initiated, phase I dose escalation trial, termed ENABLE, will investigate the safety and preliminary efficacy of WZTL-002, comprising autologous T-cells expressing a 3G anti-CD19 CAR incorporating the intracellular signalling domains of CD28 and Toll-like receptor 2 (TLR2) for the treatment of r/r B-NHL., Methods and Analysis: Eligible participants will be adults with r/r B-NHL including diffuse large B-cell lymphoma and its variants, follicular lymphoma, transformed follicular lymphoma and mantle cell lymphoma. Participants must have satisfactory organ function, and lack other curative options. Autologous T-cells will be obtained by leukapheresis. Following WZTL-002 manufacture and product release, participants will receive lymphodepleting chemotherapy comprising intravenous fludarabine and cyclophosphamide. A single dose of WZTL-002 will be administered intravenously 2 days later. Targeted assessments for cytokine release syndrome and immune cell effector-associated neurotoxicity syndrome, graded by the American Society Transplantation and Cellular Therapy criteria, will be made. A modified 3+3 dose escalation scheme is planned starting at 5×10 4  CAR T-cells/kg with a maximum dose of 1×10 6  CAR T-cells/kg. The primary outcome of this trial is safety of WZTL-002. Secondary outcomes include feasibility of WZTL-002 manufacture and preliminary measures of efficacy., Ethics and Dissemination: Ethical approval for the study was granted by the New Zealand Health and Disability Ethics Committee (reference 19/STH/69) on 23 June 2019 for Protocol V.1.2. Trial results will be reported in a peer-reviewed journal, and results presented at scientific conferences or meetings., Trial Registration Number: NCT04049513., Competing Interests: Competing interests: Trial principal investigator, RW, and co-investigator, PG, are employees of the Malaghan Institute of Medical Research, a charitable research institute and study sponsor. The other co-investigators have no competing interests to declare. PL has proprietary interest in the intellectual property of the 1928T2z construct. CB is co-Founder and Scientific Advisory Board Member of Mana Therapeutics is on the Advisory Board of Cellectis, has Stock ownership in Torque Therapeutics and Neximmune and is a Board Member of Caballeta Bio., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Infections affect about 30-50% of intensive care unit patients resulting in substantial morbidity and mortality. Multimodal interventions proved to be successful in the prevention of healthcare-associated infections. Appropriate hand hygiene including correct disinfection technique and timing is essential. Aim: The aim of our study was to investigate the hand hygiene practice among the intensive care unit healthcare workers by immediate feedback system implementation and compliance study. Method: A 3-week-long observational study was conducted at the Department of Anaesthesiology and Intensive Therapy, Semmelweis University, during November and December, 2018. Data regarding hand hygiene technique were collected by using the Semmelweis Scanner technology, while compliance data were recorded by direct observations. Statistical analysis was performed by Kruskal-Wallis test, Fisher's exact test and χ 2 -test. Results: 604 measurements were recorded by the electronic system. Hand disinfection was appropriate in 86.5% of cases. The median value of coverage was 99.87%. The trend of these indices showed persistently high values. A lower error rate was observed in the physiotherapy group compared to others (doctors: p<0.01, nurses: p = 0.03, assistant nurses: p = 0.03). 162 opportunities were recorded during direct observations. The mean compliance rate was 60.49%, with the lowest among doctors (53.97%). The difference was non-significant compared to nurses (62.92%, p = 0.26). Conclusions: Hand hygiene technique during the study period was found to be highly and permanently appropriate, while compliance was lower than expected. The immediate feedback system may be useful in achieving appropriate hand disinfection technique, although further interventions are needed for higher compliance rates. Orv Hetil. 2019; 160(49): 1957-1962.

In Germany, a regional social health insurance fund provides an integrated care program for patients with schizophrenia (IVS). Based on routine data of the social health insurance, this evaluation examined the effectiveness and cost-effectiveness of the IVS compared to the standard care (control group, CG). The primary outcome was the reduction of psychiatric inpatient treatment (days in hospital), and secondary outcomes were schizophrenia-related inpatient treatment, readmission rates, and costs. To reduce selection bias, a propensity score matching was performed. The matched sample included 752 patients. Mean number of psychiatric and schizophrenia-related hospital days of patients receiving IVS (2.3 ± 6.5, 1.7 ± 5.0) per quarter was reduced, but did not differ statistically significantly from CG (2.7 ± 7.6, 1.9 ± 6.2; p = 0.772, p = 0.352). Statistically significant between-group differences were found in costs per quarter per person caused by outpatient treatment by office-based psychiatrists (IVS: €74.18 ± 42.30, CG: €53.20 ± 47.96; p < 0.001), by psychiatric institutional outpatient departments (IVS: €4.83 ± 29.57, CG: €27.35 ± 76.48; p < 0.001), by medication (IVS: €471.75 ± 493.09, CG: €429.45 ± 532.73; p = 0.015), and by psychiatric outpatient nursing (IVS: €3.52 ± 23.83, CG: €12.67 ± 57.86, p = 0.045). Mean total psychiatric costs per quarter per person in IVS (€1117.49 ± 1662.73) were not significantly lower than in CG (€1180.09 ± 1948.24; p = 0.150). No statistically significant differences in total schizophrenia-related costs per quarter per person were detected between IVS (€979.46 ± 1358.79) and CG (€989.45 ± 1611.47; p = 0.084). The cost-effectiveness analysis showed cost savings of €148.59 per reduced psychiatric and €305.40 per reduced schizophrenia-related hospital day. However, limitations, especially non-inclusion of costs related to management of the IVS and additional home treatment within the IVS, restrict the interpretation of the results. Therefore, the long-term impact of this IVS deserves further evaluation.

Vaccines that elicit targeted tumor antigen-specific T-cell responses have the potential to be used as adjuvant therapy in patients with high risk of relapse. However, the responses induced by vaccines in cancer patients have generally been disappointing. To improve vaccine function, we investigated the possibility of exploiting the immunostimulatory capacity of type 1 Natural killer T (NKT) cells, a cell type enriched in lymphoid tissues that can trigger improved antigen-presenting function in dendritic cells (DCs). In this phase I dose escalation study, we treated eight patients with high-risk surgically resected stage II-IV melanoma with intravenous autologous monocyte-derived DCs loaded with the NKT cell agonist α-GalCer and peptides derived from the cancer testis antigen NY-ESO-1. Two synthetic long peptides spanning defined immunogenic regions of the NY-ESO-1 sequence were used. This therapy proved to be safe and immunologically effective, inducing increases in circulating NY-ESO-1-specific T cells that could be detected directly ex vivo in seven out of eight patients. These responses were achieved using as few as 5 × 10 5 peptide-loaded cells per dose. Analysis after in vitro restimulation showed increases in polyfunctional CD4 + and CD8 + T cells that were capable of manufacturing two or more cytokines simultaneously. Evidence of NKT cell proliferation and/or NKT cell-associated cytokine secretion was seen in most patients. In light of these strong responses, the concept of including NKT cell agonists in vaccine design requires further investigation.

Ex vivo generated monocyte-derived dendritic cell (moDC)-vaccines have long been touted as promising immunotherapeutic agents for cancer treatment, although the response rate generally remains low. The reasons for this are still unclear and confounded by the diversity in manufacturing protocols that may affect moDC function. Preclinical studies have shown that the stimulatory function of dendritic cells can be improved by engaging invariant NKT cells in vivo through the presentation of the glycolipid alpha-galactosylceramide via CD1d. However, expression of CD1d on moDC has been shown to be negatively correlated with expression of CD1a, which in turn has been suggested to be a surrogate marker for IL-12 secreting type-1 polarized moDC, the preferred functional characteristics for cancer vaccines. Here we challenge this notion by showing that plasma-derived lipids drive functional levels of CD1d expression, while CD1a expression can vary considerably in these cells without being correlated with a loss of polarization or immunogenicity.

Bone morphogenetic protein 15 (BMP15) is a key intraovarian growth factor regulating mammalian fertility, yet expression and localisation of different BMP15 protein forms within ovarian follicles around the time of the preovulatory LH surge remains unclear. Using immunoblotting and immunocytochemistry, the present study identified that post-translationally processed BMP15 proregion and mature proteins are increasingly expressed and localised with cumulus and granulosa cells from mice treated with pregnant mare's serum gonadotropin (PMSG) + human chorionic gonadotrophin (hCG). However, this increased expression was absent in cumulus-oocyte complexes matured in vitro. Pull-down assays further revealed that the recombinant BMP15 proregion is capable of specific interaction with isolated granulosa cells. To verify an oocyte, and not somatic cell, origin of Bmp15 mRNA and coregulated growth differentiation factor 9 (Gdf9), in situ hybridisation and quantitative polymerase chain reaction results confirmed the exclusive oocyte localisation of Bmp15 and Gdf9, regardless of treatment or assay method. Relative oocyte expression levels of Bmp15 and Gdf9 decreased significantly after PMSG + hCG treatment; nevertheless, throughout all treatments, the Bmp15:Gdf9 mRNA expression ratio remained unchanged. Together, these data provide evidence that the preovulatory LH surge leads to upregulation of several forms of BMP15 protein secreted by the oocyte for putative sequestration and/or interaction with ovarian follicular somatic cells.

There is no standard treatment for recurrent glioblastoma multiforme (GBM). Retreatment with temozolomide (TMZ) is one treatment option. We reasoned this could be more effective if combined with a vaccine that preferentially targeted TMZ-resistant cells. To test the feasibility and safety of such an approach, a phase 1 trial was conducted in which patients with GBM tumors relapsing after standard chemoradiotherapy were retreated with TMZ in combination with a vaccine consisting of monocyte-derived dendritic cells (DC) pulsed with autologous tumor cells that had previously been exposed to TMZ in vivo in the course of primary treatment. Of 14 participants, nine patients completed the initial phase of priming vaccinations and two cycles of TMZ, one proved to have radionecrosis, one rapidly progressed, and in three the yield of DC vaccine was insufficient to proceed with treatment. Other than expected toxicities related to TMZ, there were no adverse events attributable to the combined treatment. Two patients had objective radiological responses. Six month progression-free survival was 22 %, similar to retreatment with TMZ alone. Anti-tumor immune responses were assessed in peripheral blood mononuclear cells using interferon-γ ELISpot, with two patients meeting criteria for a vaccine-induced immune response, one of whom remained disease-free for nearly three years. Another patient with an anti-tumor immune response at baseline that was sustained post-vaccination experienced a 12-month period of progression-free survival. In summary, the combined treatment was safe and well-tolerated but feasibility in the recurrent setting was marginal. Evidence of immune responses in a few patients broadly correlated with better clinical outcome.