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Advanced colon cancer is a malignancy with poor response to various treatment modalities including ionising radiation (IR) and chemotherapy. Both IR and chemotherapeutic agents have been shown to act by inducing apoptosis, a type of cell death antagonised by the Bcl-xL gene product. Since approximately 60% of human colon cancers express Bcl-xL, it was the aim of this study to explore the potential of Bcl-xL antisense oligonucleotides as a novel radiosensitisation strategy. Caco-2 colon cancer cells were treated with Bcl-xL antisense oligonucleotides in combination with IR or cisplatin, and Bcl-xL protein expression, apoptosis, cell viability and clonogenic survival were examined. Bcl-xL antisense oligonucleotide specifically reduced the Bcl-xL protein level by almost 50% in Caco-2 cells. The decreased threshold for the induction of apoptosis resulted in a 300% increase of apoptosis after IR or cisplatin treatment and led to a 60% reduction of cell proliferation beyond response rates achieved with IR. These data suggest that Bcl-xL is an important factor contributing to the treatment resistance of human colon cancer. Specific reduction of Bcl-xL protein levels by antisense oligonucleotides qualifies as a promising therapeutic strategy for colon cancer that may help overcome resistance and improve clinical outcome in this malignancy.British Journal of Cancer (2003) 89, 1352-1357. doi:10.1038/sj.bjc.6601254 www.bjcancer.com [ABSTRACT FROM AUTHOR]

Purpose: The decision regarding the timepoint of a return to sports after anterior cruciate ligament (ACL) reconstruction is complex and depends on many factors, including objectively tested physical and psychological readiness as well as biological healing. The aim of this study was to investigate the influence of repetitive extracorporeal shockwave therapy (ESWT) on return-to-sports duration, clinical results and MRI results after ACL reconstruction with hamstring tendons (HT)., Material and Methods: In this prospective controlled study, all patients with acute ACL ruptures were treated by ACL reconstruction with HT. Patients were randomized into two groups (Group A: ESWT group; Group B: control group). Patients in the ESWT group received focused shockwave therapy 4, 5 and 6 weeks after ACL surgery. Follow-up investigations including IKDC score, Lysholm score, VAS and evaluation regarding return-to-sports timepoints that were conducted 3-, 6-, 9- and 12-months post-operation. An MRI investigation was performed 12-months post-operation and graft maturation (signal intensity ratio (SIR)) as well as femoral and tibial tunnel characteristics (bone marrow oedema, tunnel fluid effusion) were assessed., Results: In total, 65 patients (27.65 ± 7.07 years; 35 male/30 female) were included in this study. The mean timepoint for "return-to-pivoting-sports" was 27.92 weeks (±2.99) in the ESWT group as well as 42.64 weeks (±5.18) in the control group ( p < 0.001). In the ESWT group 31 patients (vs., Control Group: n = 6) attained the "pre-injury activity level", whereas 6 patients (vs., Control Group: n = 22) did not reach this level within 12 months post-operation. The IKDC score, Lysholm score, and VAS showed significant improvement in the ESWT group compared with the control group for all time-points ( p < 0.001). The mean SIR in the ESWT group revealed 1.81 (±0.88), whereas the control group showed a mean SIR of 2.68 (±1.04) ( p < 0.01)., Discussion: In conclusion, this is the first study investigating the effect of repetitive ESWT on ACL reconstruction with clinical outcome measurements, including the duration of return-to-sports activity and an MRI follow-up examination. Return-to-sports parameters, clinical scores and graft maturation were significantly improved in the ESWT group. This study may support an earlier return-to-sports timepoint by ESWT and is of high clinical relevance as ESWT is a cost-effective treatment option with no relevant side effects.

Background: Discrepancies between the outcomes of cancer patients between Western European and Central and Eastern European (CEE) countries have often been observed. Despite the enormous economic and civilizational progress made in these countries after the abolishment of the communist regime, structural problems persist., Summary: The present article reviews the domains of medical oncology education, human resources in oncology, cancer care, and clinical research in CEE in order to comprehensively assess the current situation and needs, describe important initiatives, and also propose ways to improving cancer outcomes in the region. Activities are under way to address these issues in national action plans to divert funding into oncology-related education, research, the purchase of equipment, and the attainment of modern hospital organization and structures., Key Message: Over the past more than 30 years, CEE countries have made enormous economic and societal progress. Nevertheless, challenges especially in the health care sector persist., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Purpose: To establish a transborder virtual tumor board (VTB) fostering state-of-the-art management of cancer patients by exchanging knowledge and expertise among oncologists in Central and Southeastern Europe (CEE)., Methods: We established and implemented a VTB based on the WebEx platform. This allowed for password-protected and secure upload of patient cases to be presented and discussed among colleagues from various oncology centers scattered throughout CEE in order to arrive at a recommendation for further diagnoses and/or treatment., Results: A total of 73 cases from 16 oncology centers located in 11 CEE countries were uploaded by 22 physicians; 71 were discussed over the course of 17 virtual meetings between June 2018 and May 2019 and 12 different kinds of malignant diseases were discussed with lung cancer (46.6%), melanoma (19.2%) and bladder cancer (13.6%) being the most commonly presented tumor entities. Of the discussed patients, 93.3% had stage IV disease at the time of presentation, 62.6% received chemotherapy or targeted treatment and 67.1% were treated with immune checkpoint inhibitors (ICPIs). The most common causes for presentation and discussion of patient cases were related to the use of ICPIs (80%)., Conclusion: When the need for expertise exceeds locally available resources, web-based VTBs provide a feasible way to discuss patient cases and arrive at conclusions regarding diagnoses and/or treatment across large geographic distances. Moreover, VTBs provide an innovative way for proper, state-of-the-art management of patients with malignant diseases in times of social distancing and the resulting need for restricted interaction during the current SARS-CoV‑2 (severe acute respiratory syndrome coronavirus type 2) pandemic., (© 2022. The Author(s).)

Background: Extravasation during chemotherapy administration can lead to dangerous adverse effects ranging from pain to tissue necrosis. Evidence-based data about prevention and treatment of extravasation injuries of some clinically used compounds still remains elusive. This work aimed to investigate, in a preclinical mouse model, the effects of extravasation of two chemotherapeutic agents, nanoliposomal irinotecan (nal-Iri) and trabectedin. In addition, we aimed to study treatment options for injuries induced by extravasation of these substances. Methods: Mice were subcutaneously injected with nal-Iri or trabectedin applied in clinically used concentration. Doxorubicin was used as a positive control. In subsequently performed experiments, hyaluronidase, DMSO and tacrolimus were tested as potential treatments against extravasation-induced injuries by trabectedin. Systemic effects were analyzed by observation and documentation of the health status of mice and local reactions were measured and graded. In addition, hematoxylin-eosin stained histological sections of the treated skin areas were analyzed. Results: Of the two tested substances, only trabectedin showed vesicant effects. Subcutaneous injection of trabectedin caused erythema formation in mice by day two that was progressing to skin ulcerations by day five. Furthermore, we found that topical treatment of mice with tacrolimus or DMSO reduced the vesicant effects of trabectedin. The results observed in vivo were supported microscopically by the analysis of histological sections. Conclusions: We recommend classifying trabectedin as a vesicant agent and nal-Iri as a non-vesicant agent. Furthermore, our results obtained in a preclinical model suggest that tacrolimus and DMSO might be suitable treatment options of trabectedin extravasations, a finding that might be further utilized in clinical studies., 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., (Copyright © 2022 Keritam, Juhasz, Schöfer, Thallinger, Aretin, Schabbauer, Breuss, Unseld and Uhrin.)

Background: An earlier analysis of the PEARL phase III study showed that palbociclib plus endocrine therapy (ET) does not improve progression-free survival (PFS) over capecitabine in aromatase inhibitor-resistant, hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC) patients. Here, we report the final overall survival (OS) analysis., Methods: Postmenopausal patients (N = 601) were randomized 1:1 to capecitabine or palbociclib plus ET (exemestane, Cohort 1; fulvestrant, Cohort 2). OS was analysed in Cohort 2, the wild-type ESR1 population and the overall population. Additionally, we analysed subsequent systemic therapies and explored PFS2 (time from randomization to the end of the first subsequent therapy/death)., Results: OS was 31.1 months for palbociclib plus fulvestrant and 32.8 months for capecitabine (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 0.81-1.50, P = 0.550). In the wild-type ESR1 population, OS was 37.2 months for palbociclib plus ET and 34.8 months for capecitabine (aHR 1.06, 95% CI 0.81-1.37, P = 0.683). In OS analyses, no subgroup showed superiority for palbociclib plus ET over capecitabine. OS in the overall population was 32.6 months for palbociclib plus ET and 30.9 months for capecitabine (P = 0.995). Subsequent systemic therapy was given to 79.8% and 82.9% of patients with palbociclib plus ET and capecitabine, respectively. Median PFS2 was similar between study arms (Cohort 2, P = 0.941; wild-type ESR1 population, P = 0.827). No new safety findings were observed., Conclusions: Palbociclib plus ET did not show a statistically superior OS compared to capecitabine in MBC patients progressing on aromatase inhibitors., Trial Registration: NCT02028507 (ClinTrials.gov), 2013-003170-27 (EudraCT)., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M. Martín has received consulting fees from AstraZeneca, Amgen, Taiho Oncology, Roche/Genentech, Novartis, PharmaMar, Eli Lilly, PUMA, Taiho Oncology and Pfizer; speakers' honoraria from AstraZeneca, Amgen, Roche/Genentech, Novartis, Daiichi-Sankyo and Pfizer; contracted research fees from Roche, Novartis and PUMA. C. Zielinski has received consulting fees and speaker's honoraria from Roche, Novartis, Bristol-Myers Squibb, Merck Sharp & Dohme, Imugene, Ariad, Pfizer, Merrimack, Merck KGaA, Fibrogen, AstraZeneca, Tesaro, Gilead, Servier, Shire, Eli Lilly and Athenex. His institution, Central European Cancer Center, Wiener Privatklinik Hospital, has received fees from Bristol-Myers Squibb, Merck Sharp & Dohme, Pfizer, AstraZeneca and Merck KGaA. M. Ruiz-Borrego has received speaker fees and advisory grants from Pfizer, Novartis and Lilly. E. Carrasco, who has a stock and other ownership interests from Lilly, has received travel and accommodation support from Roche, and her husband, who has participated in consulting and advisory board activities with Bristol-Myers Squibb, Novartis, Celgene, Roche Pharma, Janssen, Amgen, Incyte, Abbvie and Pfizer, has received travel and accommodation support from Celgene, Novartis and Bristol-Myers Squibb. His institution has received research funding from Celgene, Janssen, Bristol-Myers Squibb, Novartis, Celgene, Roche/Genentech, Amgen, Pfizer and Abbvie. GEICAM has received research funding from Roche/Genentech, Bristol-Myers Squibb, Novartis, Pfizer, Celgene, AstraZeneca, Merck Sharp & Dohme, Pierre Fabre and Takeda. E. M. Ciruelos has received advisory board honoraria from Lilly, Novartis, MSD, AstraZeneca, Pfizer and Roche; speakers' honoraria from Roche, Lilly and Pfizer; travel and congress assistance support from Pfizer and Roche. M. Muñoz has received advisory board honoraria from Pierre Favre and Seagen; honoraria for expert testimony from Novartis, Roche and Eisai; travel and congress assistance support from Roche, Novartis, Pfizer and Eisai. B. Bermejo has received advisory board honoraria from Roche, Novartis and MSD; speakers' honoraria from Roche, Novartis, MSD, Pfizer and Pierfabre; travel and congress assistance support from Pfizer. M. Margelí has received advisory board fees from Roche, Novartis, Pfizer and Eisai. Her institution, ICO-Badalona. B-ARGO (Badalona Applied Research Group in Oncology) Hospital Universitari Germans Trias i Pujol, Badalona, has received funding research from Roche, Pfizer, Novartis, Lilly, AstraZeneca, Eisai and Kern, and she has received travel and congress assistance support from Roche. A. Antón has received advisory board fees from Bayer Spain, Lilly and Gilead. N. Turner has received advisory board honoraria from Astra Zeneca, Bristol-Myers Squibb, Lilly, Merck Sharp & Dohme, Novartis, Pfizer, Roche/Genentech, Bicycle Therapeutics, Taiho, Zeno pharmaceuticals and Repare; therapeutics and research funding from Astra Zeneca, BioRad, Pfizer, Roche/Genentech, Clovis, Merck Sharp & Dohme and Guardant Health. E. Alba has received advisory board fees from Roche, Novartis, Pfizer, Lilly, Bristol-Myers Squibb, Genomic Health and Nanostring. He has received travel support from Celgene. His institution, Hospitales Regional y Virgen de la Victoria, Málaga, has received funding research from Roche, Pfizer, Sysmex, Merck Sharp & Dohme and Nanostring. J. de la Haba-Rodríguez has received speaker's honoraria from AstraZeneca, Pfizer, Novartis and Lilly. M. Ramos has received honoraria from Novartis, Roche and Pfizer. M. Corsaro is employed by Pfizer and has company stock options. X. Huang is employed by Pfizer and has company stock options. Z. Kahan has participated in advisory boards of and received speaker fees or travel support from Pfizer, Roche, AstraZeneca and Novartis. M. Gil-Gil has received honoraria from Pfizer, Ferrer International and Esteve Pharma. All remaining authors have declared no conflicts of interest. A complete list of the PEARL trial collaborators is provided in the Supplementary Appendix., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Novel treatment modalities like targeted therapy and immunotherapy are currently changing treatment strategies and protocols in the field of medical oncology., Methods: Numbers of patients and patient contacts admitted to medical oncology day clinics of a large European academic cancer centre in the period from 2006 to 2018 were analysed using our patient administration system., Results: A patient cohort of 9.870 consecutive individual patients with 125.679 patient contacts was descriptively and retrospectively characterised. Mean age was 59.9 years. A substantial increase in both individual patients treated per year (+45.4%; 2006: 1.100; 2018: 1.599) and annual patient contacts (+63.3%; 2006: 8.857; 2018: 14.467) between 2006 and 2018 was detected. Hence and most interestingly, the ratio of visits per patient increased by approximately one visit per patient per year over the last 12 years (+12.4%; 2006: 8.0; 2018: 9.0). Further, a decrease of patient contacts in more prevalent entities like breast cancer was found, while contacts for orphan diseases like myeloma and sarcoma increased substantially. Interestingly, female patients showed more per patient contacts as compared with men (13.5 vs 11.9). Lastly, short-term safety data of outpatient day clinic admissions are reported., Conclusions: We present a representative and large set of patient contacts over time that indicates an increasing load in routine clinical work of outpatient cancer care. Increases observed were highest for orphan diseases, likely attributed to centralisation effects and increased treatment complexity., Competing Interests: Competing interests: MM has received honoraria for lectures and consultation from Roche, Novartis, Eli-Lilly and Medmedia and travel support from Amgen, Roche, Novartis, Pierre Fabre, Daiichi Sankyo and Eisai. RB was an advisor for Astra-Zeneca, Celgene, Daiichi, Eisai, Eli-Lilly, MSD, Novartis, Pfizer, Pierre-Fabre, Puma, Roche and Samsung and received lecture honoraria from Accord, Astra-Zeneca, BMS, Celgene, Eli-Lilly, Novartis, Pfizer, Pierre-Fabre, Roche, Sandoz as well as research support from Daiichi, Novartis and Roche. MP has received honoraria for lectures, consultation or advisory board participation from the following for-profit companies: Bayer, Bristol-Myers Squibb, Novartis, Gerson Lehrman Group (GLG), CMC Contrast, GlaxoSmithKline, Mundipharma, Roche, BMJ Journals, MedMedia, Astra Zeneca, AbbVie, Lilly, Medahead, Daiichi Sankyo, Sanofi, Merck Sharp & Dome, Tocagen. The following for-profit companies have supported clinical trials and contracted research conducted by MP with payments made to his institution: Böhringer-Ingelheim, Bristol-Myers Squibb, Roche, Daiichi Sankyo, Merck Sharp & Dome, Novocure, GlaxoSmithKline, AbbVie. ASB has research support from Daiichi Sankyo (≤ €10 000), Roche (> €10 000) and honoraria for lectures, consultation or advisory board participation from Roche Bristol-Meyers Squibb, Merck, Daiichi Sankyo (all <€5000) as well as travel support from Roche, Amgen and AbbVie. TB reports personal fees from Bayer (lecture fee, advisory board), personal fees from PharmaMar (lecture fee, advisory board), personal fees from Eli-Lilly (lecture fee, advisory board) outside the submitted work. SZ-M received honoraria for advisory boards and/or lectures from Boehringer Ingelheim, Merck Sharp & Dohme, Bristol Myers Squibb, Roche, AstraZeneca, Takeda and Pfizer. Research support to her was granted by Merck Sharp & Dohme. TF hast received honoraria from MSD, Merck Darmstadt, Roche, BMS, Accord, Sanofi, Boehringer Ingelheim, Novartis and was and advisor or consultant for MSD; Merck Darmstadt, Amgen, Pfizer, Sanofi and Boehringer Ingelheim. He has further received travel expenses, including accommodations, from Roche, MS and BMS as well as research grants or funding from MSD, Merck Darmstadt. AI-M announces following COIs: Participation at advisory boards of MSD, Servier and BMS, lecture honoraria from Eli Lilly and Servier and travel support from Roche and BMS. She has also served as local PI for clinical trials sponsored by BMS and Astellas. All other authors report no relevant conflicts of interest., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Background: Treatment of non-small cell lung cancer (NSCLC) improved substantially in the last decades. Novel targeted and immune-oncologic drugs were introduced into routine treatment. Despite accelerated development and subsequent drug registrations by the European Medicinal Agency (EMA), novel drugs for NSCLC are poorly accessible in Central and Eastern European (CEE) countries., Material and Methods: The Central European Cooperative Oncology Group conducted a survey among experts from 10 CEE countries to provide an overview on the availability of novel drugs for NSCLC and time from registration to reimbursement decision in their countries., Results: Although first-generation epidermal growth factor receptor tyrosine kinase inhibitors were reimbursed and available in all countries, for other registered therapies-even for ALK inhibitors and checkpoint inhibitors in first-line-there were apparent gaps in availability and/or reimbursement. There was a trend for better availability of drugs with longer time from EMA marketing authorization. Substantial differences in access to novel drugs among CEE countries were observed. In general, the availability of drugs is not in accordance with the Magnitude of Clinical Benefit Scale (MCBS), as defined by the European Society for Medical Oncology (ESMO). Time spans between drug registrations and national decisions on reimbursement vary greatly, from less than 3 months in one country to more than 1 year in the majority of countries., Conclusion: The access to novel drugs for NSCLC in CEE countries is suboptimal. To enable access to the most effective compounds within the shortest possible time, reimbursement decisions should be faster and ESMO MCBS should be incorporated into decision making., (© 2019 The Authors. The Oncologist published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background: The treatment of anterior glenohumeral instability with a Bankart repair combined with a capsular plication is a frequently used arthroscopic technique. Latarjet created an open bone block procedure in 1954 for the treatment of anteroinferior glenohumeral instability. This procedure has been further developed by Lafosse in 2003 for arthroscopic surgery. The aim of this study is to evaluate the clinical outcome and complications of the latter procedure, most notably infection rate and nerve damage., Materials and Methods: 132 shoulders (106 males/19 females, 68 right/64 left) were included in this retrospective study. Patients were included if treatment was performed for anterior instability and if the patient's instability severity index score was at least 4, or if a revision procedure was performed after a prior unsuccessful arthroscopic or open capsule and labral repair. Treatment included the arthroscopic transfer of the coracoid process for the anterior stabilization of the shoulder joint. The disabilities of the arm, shoulder, and hand score were evaluated postoperatively in 76 patients and compared with the results found in the literature. Mean followup was 20.1 [±14.09] months., Results: The rate of recurrent glenohumeral instability which needed revision surgery after the arthroscopic Latarjet procedure was 6.1% ( n = 8). There were no severe neurovascular complications seen in our cohort. In 32 cases, re-operation was performed due to subjective discomfort because of screw impingement or postoperative shoulder stiffness., Conclusion: The all-arthroscopic Latarjet procedure developed by Lafosse is a valid and reliable method for the treatment of shoulder instability. Our favorable results indicating that this procedure can prevent chronic shoulder luxation are repeatable, and the rate of postoperative recurrence is low., Competing Interests: There are no conflicts of interest.

This article analyzes the availability of different diagnostic procedures of non-small cell lung cancer (NSCLC) and the reimbursement landscape of drugs for NSCLC in countries of central and southeastern Europe (CEE). A survey was conducted by the Central European Cooperative Oncology Group. Results of the survey show that both availability and reimbursement of diagnoses of molecular alterations in NSCLC, the detection of which is essential for therapeutic decisions, varies widely between countries of CEE. Not only is "reflex" testing often substituted by analyses performed only "on demand," but reimbursement of such assessments varies widely between unavailability and payments by the health care system or even pharmaceutical companies. It was concluded that a structured access to testing and reimbursement should be the aim in order to provide patients with appropriate therapeutic options. IMPLICATIONS FOR PRACTICE: This article provides an overview of the limitations in lung cancer treatment in countries of central and southeastern Europe, as well as the reimbursement status of various lung cancer treatment regimens in these countries, which directly impacts treatment options., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2018.)

Immunotherapy by checkpoint inhibition is about to profoundly change cancer therapy. The number of indications are growing at an unprecedented speed. Clinical studies have demonstrated efficacy in a variety of solid tumors and in hematologic malignancies, although some clinical trials have produced negative results. Thus, it is fair to assume that there are obvious limitations and pitfalls in immunotherapy. Future concepts for combination treatment of immune checkpoint inhibitors have to be developed, but there is also urgent need for better and standardized biomarkers to identify those cancer patients who will benefit from treatment by checkpoint inhibition. The current overview summarizes current knowledge on immune checkpoint inhibitor treatment in malignancies, its outlook and limitations, diagnostic means and, finally, side effect management.

The blood-brain barrier (BBB) protects the central nervous system (CNS) from potentially harmful substances and molecules by limiting their influx from the blood stream into the brain parenchyma. Understanding the structure and functioning of the BBB is of major importance for the development of effective medical treatments for primary and secondary brain tumours. Therefore, we provide here a concise and illustrated educational description of the anatomy and physiology of the BBB and current concepts on its role for targeted cancer therapies and immuno-oncology., Competing Interests: Competing interests: None declared.

Watch the video here. Building on our previous educational video on the interaction between cancer and the immune system, we highlight in this video the role of programmed death ligand 1 (PD-L1) in the tumour microenvironment. We explain the function of important immune cell types found in the tumour microenvironment and how they interact with each other and with cancer cells. Dendritic cells take up tumour antigen and transport it to the regional lymph node for T cell priming. T cells are the main mediators of the adaptive immune system and kill tumour cells via release of cytotoxins. Macrophages are the main effector cells of the innate immune system and have various functions such as phagocytosis and antigen presentation. Therapeutic monoclonal antibodies that bind to PD-1 or PD-L1, so called immune checkpoint inhibitors, prevent the interaction of these immune-suppressive molecules and thus facilitate an effective T cell-mediated antitumour immune response.

Background: Bite wounds are among the commonest types of trauma to which man is the subject. They account for 5 % of the total traumatic wounds evaluated in the emergency department (ED) and approximately 1 % of all the ED visits. Early estimation of infection risk, adequate antibiotic therapy and if indicated surgical treatment are the cornerstones of successful cure of bite wounds., Methods: A total of 5248 consecutive trauma patients were collected prospectively and analysed retrospectively over a period of 15 years in this study at a level I trauma centre, Department of Trauma Surgery, Medical University of Vienna, Austria., Results: The mean age was 33.8 years (range 0-97), 2620 (49.9 %) were male and 2628 (50.1 %) were female individuals. In our study population, a total of 2530 dog bites (48.2 %), 930 cat bites (17.8 %), 357 other animal bites (6.8 %), 426 human bites (8.1 %) and 1005 human self-bites (19.2 %) have been observed. A total of 995 wounds (19.0 %) have been infected. Surgery was done in 132 wounds (2.5 %)., Conclusion: We could show a six times higher infection rate of cat bites compared to dog bites. Human bites showed a total infection rate of 8.2 %. Observed infection rate of puncture wounds and wounds greater than 3 cm was 1.5 times higher than for all other wounds in the present study. Total infection rates within 24 h to antibiotic administration was 29.3 %, compared to 65.0 % < 48 h and 81.1 % < 72 h. Time interval also influenced the overall outcome showing a 2.6 increase in acceptable and 1.3 increase in poor outcome after 72 h.

This educational video discusses and visualises the key steps of the complex interaction between cancer and the immune system. Essential steps of the cancer immune cycle take place in the tumour itself and in regional lymph nodes, with immune cells travelling between these distinct sites. Antigen-presenting cells such as dendritic cells migrate into the tumour microenvironment and take up tumour antigens. Antigen-presenting cells travel to regional lymph nodes, where they present the tumour antigens to naïve T cells in order to initiate a tumour-specific T cell response. Activated tumour-specific T cells multiply by clonal expansion and enter the blood flow and travel from the regional lymph node to the tumour site. As soon as activated T cells arrive at the tumor site they start a tumour-specific immune response. Co-inhibitory receptors modulate the immune response and may be exploited by tumour cells to escape immunological destruction. In summary, the cancer immune cycle involves several pivotal steps that are essential for generation of a successful specific antitumour immune response. Importantly, dysfunction of a single step may interrupt the entire cycle, thus impairing the immune-mediated control of tumour growth. Immune modulatory therapies such as vaccines or immune checkpoint modulators target specific steps of the cancer immune cycle with the ultimate aim of facilitating an antitumour immune response.

Background: Vinorelbine constitutes effective chemotherapy for metastatic breast cancer (MBC) and acts synergistically with trastuzumab in HER-2/neu positive disease. The present study was set out to evaluate the efficacy and safety of vinorelbine when combined with lapatinib, an anti-HER2 tyrosine-kinase inhibitor, as late-line regimen administered beyond previous disease progression on prior lapatinib in patients with HER-2/neu- positive MBC., Methods: The CECOG LaVie study was designed as open-labeled, single-arm, multicenter phase II trial. Patients had to be pretreated with lapatinib plus chemotherapy, and received lapatinib at a daily dose of 1250 mg in combination with vinorelbine 20 mg/m(2) i.v. on days 1 and 8 of a three-week cycle until disease progression, intolerable toxicity or withdrawal of consent. Progression-free survival (PFS) was defined as primary study endpoint; secondary endpoints included overall survival (OS), response rate according to RECIST 1.1, and safety. The study was terminated early due to poor accrual., Results: A total number of nine patients were included; lapatinib administered beyond disease progression combined with vinorelbine resulted in a median PFS of 7.7 months (95% CI 0.56-14.91) and a median OS of 23.4 months (95% CI 16.61-30.13), respectively. Partial remission was seen in one of nine patients, three patients had stable disease of > six months, whereas the remaining five patients had primary disease progression. In two patients, modification of vinorelbine dose due to toxicity became necessary; no dose modification was needed for lapatinib. The majority of reported adverse events (AE) were grade 1 and 2 in severity with diarrhea being the most commonly observed AE CONCLUSION: In this heavily pretreated patient population, combination of vinorelbine plus lapatinib showed encouraging activity and was characterized by an acceptable safety profile. Despite the low patient number, lapatinib plus vinorelbine may constitute a potential treatment option in heavily pretreated patients with HER-2/neu-positive MBC previously exposed to lapatinib., Trial Registration: EudraCT number 2009-016826-15, (15. 10.2009).

Objectives: The use of complementary and alternative medicine has increased over the past decade. The aim of this study was to evaluate whether homeopathy influenced global health status and subjective wellbeing when used as an adjunct to conventional cancer therapy., Design: In this pragmatic randomized controlled trial, 410 patients, who were treated by standard anti-neoplastic therapy, were randomized to receive or not receive classical homeopathic adjunctive therapy in addition to standard therapy. The study took place at the Medical University Vienna, Department of Medicine I, Clinical Division of Oncology., Main Outcome Measures: The main outcome measures were global health status and subjective wellbeing as assessed by the patients. At each of three visits (one baseline, two follow-up visits), patients filled in two different questionnaires., Results: 373 patients yielded at least one of three measurements. The improvement of global health status between visits 1 and 3 was significantly stronger in the homeopathy group by 7.7 (95% CI 2.3-13.0, p=0.005) when compared with the control group. A significant group difference was also observed with respect to subjective wellbeing by 14.7 (95% CI 8.5-21.0, p<0.001) in favor of the homeopathic as compared with the control group. Control patients showed a significant improvement only in subjective wellbeing between their first and third visits., Conclusion: Results suggest that the global health status and subjective wellbeing of cancer patients improve significantly when adjunct classical homeopathic treatment is administered in addition to conventional therapy., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: We compared the public perception of cancer care in Poland and Austria. Both countries are members of the European Union (EU) but reflect two extremes in health-related per capita spending. Recently, the EUROCARE-5 study reported on very discrepant cancer outcomes between the two countries., Methods: A one-time survey was conducted to compare the public perception of cancer treatment in Poland and Austria. In total, 3,649 subjects, representing the general population, cancer patients, and cancer patients' family members, were surveyed., Results: In both countries, cancer was considered the most challenging problem of the health care system, and health care was indicated as the most important issue influencing political election decisions. Polish compared with Austrian cancer patients gave a significantly lower positive assessment of overall cancer treatment efficacy and detection methods. Cancer cure rates estimated by Polish and Austrian citizens were 29% and 44%, respectively. The majority of all citizens interviewed thought that cancer patients should have access to all available registered cancer drugs. However, only 18% of Poles versus 62% of Austrians agreed with the notion that the available cancer treatment in their countries is of a standard comparable to that of other EU countries. Consequently, 24% of Poles and 7% of Austrians identified financial status, age, gender, and residence as factors influencing the availability of cancer treatments., Conclusion: In both countries, cancer is considered the most challenging problem of the health care system, and health care issues may strongly influence decisions for political elections. Vast differences in the two populations' perceptions of cancer care reflect actual cancer outcomes and the national per capita spending on health-related issues., (©AlphaMed Press.)

Background: Diagnosis and early treatment of developmental dysplasia of the hip (DDH) continue to be issues of discussion. In 1992, a nationwide general ultrasound screening program using Graf technique was introduced to detect DDH in Austria. We investigated the effects of this program on the rates of operative and conservative interventions and the influence of the program on the number of hospital admissions for the treatment of DDH., Methods: All cases of DDH documented in Austrian hospitals from 1992 to 2008 were included in this retrospective study. The database of the Austrian Ministry of Health was used to extract documented diagnoses and treatments., Results: Since the introduction of the screening program, the number of patients who require pelvic surgery to treat DDH has decreased by 46 % and the number of open reductions is as low as 0.16 per 1,000 live births. Hospital admissions for the treatment of DDH decreased from 9.5 to 3.6 per 1,000 live births. All noted results gained statistical significance., Conclusion: Compared with routine clinically based screening programs, our results confirm low numbers of open reductions and pelvic surgeries. We, therefore, advocate a standardized nationwide general ultrasound screening program to reduce the rates of operative interventions and hospital admissions associated with the treatment of DDH., Level of Evidence: Level III, diagnostic.

Anaplastic large cell lymphoma (ALCL) is an aggressive non-Hodgkin's lymphoma found in children and young adults. ALCLs frequently carry a chromosomal translocation that results in expression of the oncoprotein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). The key molecular downstream events required for NPM-ALK-triggered lymphoma growth have been only partly unveiled. Here we show that the activator protein 1 family members JUN and JUNB promote lymphoma development and tumor dissemination through transcriptional regulation of platelet-derived growth factor receptor-β (PDGFRB) in a mouse model of NPM-ALK-triggered lymphomagenesis. Therapeutic inhibition of PDGFRB markedly prolonged survival of NPM-ALK transgenic mice and increased the efficacy of an ALK-specific inhibitor in transplanted NPM-ALK tumors. Notably, inhibition of PDGFRA and PDGFRB in a patient with refractory late-stage NPM-ALK(+) ALCL resulted in rapid, complete and sustained remission. Together, our data identify PDGFRB as a previously unknown JUN and JUNB target that could be a highly effective therapy for ALCL.

Background/aims: We measured the extracellular concentrations of fluconazole in lung tissue of septic and healthy rats., Methods: A single intravenous dose of 6 mg/kg total body weight of fluconazole was administered intravenously to rats following insertion of microdialysis probes into lung tissue. Another probe was inserted into skeletal muscle and served as control., Results: The mean peak concentration (C(max)), time to C(max), area under the concentration-versus-time curve from 0 to 6 h (fAUC(0-6)) and area under the concentration-versus-time curve from 0 to ∞ of unbound fluconazole for healthy lung were 11.0 ± 2.3 mg/l, 1.9 ± 1.5 h, 47.4 ± 8.6 mg·h/l and 233.7 ± 121.1 mg·h/l, respectively. The corresponding values for inflamed lung were 11.8 ± 1.7 mg/l, 1.5 ± 0.0 h, 52.9 ± 6.2 mg·h/l and 212.6 ± 79.7 mg·h/l, respectively. The mean apparent terminal elimination half-lives of fluconazole ranged from 12.3 to 22.4 h between compartments. The ratios of the fAUC(0-6) for lung to the fAUC(0-6) for plasma were 1.38 ± 0.39 and 1.32 ± 0.04 for healthy and inflamed lung, respectively., Conclusion: We provide evidence that free fluconazole levels in plasma, the extracellular space fluid of lung tissue and skeletal muscle are almost superimposable during inflammatory and normal conditions., (Copyright © 2011 S. Karger AG, Basel.)

Aberrant anaplastic lymphoma kinase (ALK) expression is a defining feature of many human cancers and was identified first in anaplastic large-cell lymphoma (ALCL), an aggressive non-Hodgkin T-cell lymphoma. Since that time, many studies have set out to identify the mechanisms used by aberrant ALK toward tumorigenesis. We have identified a distinct profile of micro-RNAs (miRNAs) that characterize ALCL; furthermore, this profile distinguishes ALK(+) from ALK(-) subtypes, and thus points toward potential mechanisms of tumorigenesis induced by aberrant ALK. Using a nucleophosmin-ALK transgenic mouse model as well as human primary ALCL tumor tissues and human ALCL-derived cell lines, we reveal a set of overlapping deregulated miRNAs that might be implicated in the development and progression of ALCL. Importantly, ALK(+) and ALK(-) ALCL could be distinguished by a distinct profile of "oncomirs": Five members of the miR-17-92 cluster were expressed more highly in ALK(+) ALCL, whereas miR-155 was expressed more than 10-fold higher in ALK(-) ALCL. Moreover, miR-101 was down-regulated in all ALCL model systems, but its forced expression attenuated cell proliferation only in ALK(+) and not in ALK(-) cell lines, perhaps suggesting different modes of ALK-dependent regulation of its target proteins. Furthermore, inhibition of mTOR, which is targeted by miR-101, led to reduced tumor growth in engrafted ALCL mouse models. In addition to future therapeutical and diagnostic applications, it will be of interest to study the physiological implications and prognostic value of the identified miRNA profiles.

Based on clinicians' expectations of high concentrations of telithromycin (TEL) in tissues, combined with its excellent in vitro antimicrobial characteristics, TEL is casually considered as a potential therapeutic option for the therapy of minor cases of soft tissue or bite-wound infections. To clarify this clinically important issue, the present investigation was carried out to measure the pharmacokinetic profile of TEL in the interstitial space fluid (ISF) of skeletal muscle and subcutaneous adipose tissue by means of the microdialysis technique in 10 healthy subjects following repetitive daily doses of 800 mg TEL. These data were compared with free concentrations of TEL determined in plasma. External controls for the present examination were the use of historic, single-dose data collected by our study group utilising identical methods and the same trial subjects. Despite an increase in the median half-life from ca. 3 h after a single dose to ca. 10h at steady-state conditions in all compartments, accumulation of TEL in ISF of soft tissues and plasma was clinically non-relevant. Median free peak concentrations in plasma, skeletal muscle and subcutis were 0.52, 0.13 and 0.19 mg/L, respectively. The median ratios of the tissue to plasma free areas under the concentration-time curves from 0 to 24 h (fAUC(0-24) tissue/fAUC(0-24) plasma) were 0.27 and 0.58 for muscle and subcutis, respectively (P>0.05). The present multiple-dose investigation of TEL is in line with a previous single-dose study confirming that TEL 800 mg/day may not be optimally effective in the therapy of soft tissue infections.

In previous studies, tetracyclines have been shown to decrease the release of cytokines in experimental settings of endotoxaemia. Tigecycline is the first member of the closely related glycylglycines and, due to its broad antimicrobial spectrum, it is considered useful in the treatment of sepsis. We therefore tested its ability to influence the concentrations of the proinflammatory cytokines interleukin (IL)-1beta, tumour necrosis factor-alpha (TNFalpha) and IL-6 in an established ex vivo model of human endotoxaemia. Whole blood from ten healthy volunteers was incubated with either saline (negative control), tigecycline (1 microg/mL [therapeutic concentration] or 100 microg/mL [supratherapeutic concentration]), lipopolysaccharide (LPS; 50 pg/mL, control) or a combination of tigecycline plus LPS (test group). Concentrations of IL-1beta, TNFalpha and IL-6 in the supernatant were measured using commercially available enzyme-linked immunosorbent assay (ELISA) kits. As expected, incubation with LPS significantly increased the cytokine concentrations in whole blood compared with baseline (P<0.05). The combination of tigecycline plus LPS did not exert any significant effect on the concentrations of IL-1beta, IL-6 and TNFalpha after 2h and 4h of incubation compared with LPS alone. These results indicate that proinflammatory cytokines remained unaffected by tigecycline in an established ex vivo model of systemic inflammatory response.

By utilizing the microdialysis technique, we investigated the pharmacokinetic profile of voriconazole in the interstitium of the lungs and skeletal muscle tissue of rats after a single intravenous dose under healthy and inflammatory conditions. As expected, voriconazole penetrated excellently into the interstitium of tissues, and its levels were descriptively almost identical to free concentration-versus-time profiles in plasma.