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  Karger Kompass
   Full-text available via subscription Subscription journal
   ISSN (Print) 2296-0368 - ISSN (Online) 2296-0317
   Published by Karger Homepage  [104 journals]
  • NADIR: A Non-Interventional Study on the Prophylaxis of
           Chemotherapy-Induced Neutropenia Using Lipegfilgrastim - First Interim
    • Abstract: Background: The non-interventional study (NIS) NADIR was designed to assess the effectiveness and safety of lipegfilgrastim, a novel glycopegylated granulocyte-colony stimulating factor, in reducing the risk of both febrile and severe neutropenia. Methods: Here, the interim analysis of NIS Nadir performed under real-world conditions at 80 oncology practices across Germany is reported. For a patient to be included, lipegfilgrastim at a subcutaneous single dose of 6 mg had to be administered during at least 1 cycle of the chemotherapy under consideration. Results: The interim analysis included 224 patients. Median patient age was 61.1 years (interquartile range 51.2-70.2 years). Main tumor type was breast cancer followed by lung cancer, and non-Hodgkin's lymphoma (46.0, 13.4, and 10.7%, respectively). When lipegfilgrastim was given as primary prophylaxis, no patient developed febrile neutropenia (FN). 1.3% of patients developed FN when primary prophylaxis was withheld. Only 68.6% of patients undergoing chemotherapy and at high risk (> 20%) of developing FN were treated with lipegfilgrastim during the first cycle, exposing disparity between real-world practices and current treatment guidelines. Lipegfilgrastim was well tolerated. The only grade 3/4 treatment-related adverse event was anemia in 1 patient. Conclusion: Lipegfilgrastim was effective and safe when administered for the prevention of chemotherapy-induced neutropenia under real-world conditions.
      Oncol Res Treat 2015;38:221-229
  • Does Physical Activity Improve Quality of Life in Cancer Patients
           Undergoing Chemotherapy'
    • Abstract: Background: Improved cancer treatments have resulted in prolonged survival. Nevertheless, tumor symptoms and side effects still compromise physical activity and quality of life (QoL). Patients and Methods: We conducted an anonymous survey among cancer patients undergoing chemotherapy using standardized questionnaires: the ‘Freiburger Fragebogen zur körperlichen Aktivität' (Freiburg Questionnaire on Physical Activity) and European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Two main questions were addressed: were there differences (1) in physical activity and QoL between patients who do not believe that sport could improve their QoL and those who believe it could (group A vs. B); and (2) in QoL between patients with a total activity (TA) < 18 metabolic equivalent of task (MET) h/week and those with a TA of ≥ 18 MET h/week (group C vs. D)' Results: 276 of 400 questionnaires were completed. Groups A and B were balanced in terms of baseline characteristics. Group A suffered significantly more from fatigue and pain; group B reported higher levels of global health status (GHS) and TA. Groups C and D differed in gender distribution, age, and educational background. Group D had significantly higher levels of GHS, group C suffered more from fatigue, pain, and appetite loss. Conclusion: Physical activity correlates with a better QoL of cancer patients undergoing chemotherapy.
      Oncol Res Treat 2015;38:230-236
  • Pig BMSCs Transfected with Human TFPI Combat Species Incompatibility and
           Regulate the Human TF Pathway in
    and in a Rodent Model
    • Abstract: Background: The activation of tissue factor (TF) is one of the major reasons for coagulation dysregulation after pig-to-primate xenotransplantation. Tissue factor pathway inhibitor (TFPI) is the most important inhibitor of TF. Studies have demonstrated species incompatibility between pig TFPI and human TF. Methods: A pig-to-macaque heterotopic auxiliary liver transplantation model was established to determine the origin of activated TF. Chimeric proteins of human and pig TFPI were constructed to assess the role of Kunitz domains in species incompatibility. Immortalised pig bone marrow mesenchymal stem cells transfected with human TFPI were tested for their ability to inhibit clotting in vitro. Results: TF from recipient was activated early after liver xenotransplantation. Pig TFPI Kunitz domain 2 bound human FXa, but Kunitz domain 1 did not effectively inhibit human TF/FVIIa. Immortalised pig bone marrow mesenchymal cells (BMSCs) transfected with human TFPI showed a prolonged recalcification time in vitro and in a rodent model. Conclusion: Recipient TF is relevant to dysregulated coagulation after xenotransplantation. Kunitz domain 1 plays the most important role in species incompatibility between pig TFPI and human TF, and clotting can be inhibited by human TFPI-transfected pig BMSCs. Our study shows a possible way to resolve the incompatibility of pig TFPI.
      Cell Physiol Biochem 2015;36:233-249
  • Prospective Evaluation of a Transfusion Policy of RhD-Positive Red Blood
           Cells into DEL Patients in China
    • Abstract: Background: The D antigen is highly immunogenic, requiring only a small quantity of transfused red blood cells (RBCs) to cause alloimmunization in D- immunocompetent recipients. DEL was reported arousing alloimmunization to true Rh- patients. Molecular studies of the RHD gene have revealed that DEL individuals retain a grossly intact RHD gene or have a portion of RHD in their genomes. Avoiding immunization with clinically important antibodies is a primary objective in transfusion medicine. Methods: In order to determine whether pregnant DEL women carrying an RhD+ fetus are at risk of anti-D alloimmunization, 808 Rh- pregnant women with a history of gestations or parturitions who regularly visited hospitals for their prenatal anti-D screening and postpartum care from January 2011 to December 2012 were investigated. Samples were analyzed for DEL by PCR with specific primers, PCR-sequence-specific primers (PCR-SSP), reverse transcription-PCR (RT-PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and by gene sequencing to characterize different alleles. Results: Among the 808 Rh- pregnant women of our sample, 178 (22.0%) were typed as DEL; 168 DEL samples were confirmed to have the RHD (1,227 G>A) allele, 8 DEL samples were characterized by one base mutation of the RHD (3G >A) allele, and the remaining two DEL samples were determined to carry RHD-CE(4-9)-D or RHD-CE(2-5)-D. The observation of allo-anti-D in two prominent D epitope loss cases confirmed the partial nature of these DEL phenotypes. Conclusions: In conclusion, evidence is provided that different DEL genotypes code either for partial or complete D antigen expression. It is suggested that the use of RhD+ RBCs in complete D antigen DEL patients does not induce adverse reaction.
      Transfus Med Hemother
  • Monitoring of Hematopoietic Chimerism by Real-Time Quantitative PCR of
           Micro Insertions/Deletions in Samples with Low DNA Quantities
    • Abstract: Background: Sensitive and accurate methods to detect hematopoietic chimerism after hematopoietic stem cell transplantation (HSCT) are essential to evaluate engraftment and to monitor response to therapeutic procedures such as donor lymphocyte infusion. Continuous long-term follow up, however, requires large amounts of pre-HSCT samples limiting the application of many widely used techniques for sensitive chimerism monitoring. Methods: DNAs from 42 normal healthy donors and 16 HSCT donor/recipient pairs were employed to validate the use of allele-specific insertion/deletion (indel) quantitative real-time polymerase chain reaction (qPCR) to quantify chimerism in samples with low amounts of DNA. Consequently, indel-qPCR analyses of samples from 16 HSCT patients were compared to short-tandem repeat (STR) specific PCR analyses. Results: Typing with reduced amounts of input DNA (15 vs. 60 ng) allowed for the reliable distinction of positive (mean threshold cycle (ct) 28.05) and negative (ct >36) signals. The high informativity of primer/probe sets, with 12 out of 19 markers exceeding 20% informativity, was confirmed in our cohort (n = 74). Importantly, a fourfold reduction of input DNA compared to published protocols did not alter PCR efficiencies and allowed for a more sensitive detection of chimerism in 7 of 16 HSCT patients compared to results obtained by STR-PCR. Conclusions: Our data suggest that indel-qPCR is a more sensitive technique for the detection of hematopoietic chimerism compared to STR-PCR and works efficiently for samples with low amounts of DNA.
      Transfus Med Hemother
  • A Unique Case Involving a Female Patient with Upshaw-Schulman Syndrome:
           Low Titers of Antibodies against ADAMTS13 prior to Pregnancy Disappeared
           after Successful Delivery
    • Abstract: Background: Upshaw-Schulman syndrome (USS) is usually suspected based on severe deficiency of ADAMTS13 activity without ADAMTS13 antibody, but the definitive diagnosis is made by ADAMTS13 gene analysis. We present a unique case of USS with low titers of ADAMTS13 antibodies before pregnancy. Interestingly, titers of ADAMTS13 antibodies decreased to almost undetectable levels after delivery. Case Report: In patient LL4, the diagnosis of USS was confirmed at age 27 by ADAMTS13 gene analysis. She became pregnant at age 30. During the pregnancy, she received regular fresh frozen plasma (FFP) infusion. Plasma von Willebrand factor levels increase as pregnancy progresses. To prevent platelet thrombi, much more ADAMTS13 supplementation is necessary during late gestation in patients with USS. Therefore, we shortened the interval between and increased the volume of FFP infusions as pregnancy progressed. At 39 weeks, she delivered a healthy baby girl. Before pregnancy, she had low titers of both neutralizing and binding anti-ADAMTS13 antibodies. Despite frequent FFP infusions, titers of the antibodies did not increase, but rather decreased to almost undetectable levels during pregnancy. Conclusion: Both the neutralizing and binding antibodies against ADAMTS13 decreased to almost undetectable levels after delivery in this patient, which can be caused by an immunological reset.
      Transfus Med Hemother
  • Impact of Prophylactic Mastectomy in
           BRCA1/2 Mutation Carriers
    • Abstract: Unlike the general decrease in invasive oncologic care, the trend for prophylactic bilateral mastectomy in healthy women and prophylactic contralateral mastectomy in women with unilateral breast cancer is steadily rising. This is even more surprising when considering that for e.g. prophylactic contralateral mastectomy no clear survival benefit has been demonstrated so far. The decision-making process around risk-reducing surgery may be influenced by several conflicting parameters such as the patient's fears and desire to achieve a survival advantage, the surgeon's financial motivations, or the oncologist's paternalistic approach to the above trend. Physicians should support their patients throughout the decision-making process, guide them through the dense fog of information, and encourage them to reconsider all options and alternatives before embarking on an irreversible surgical intervention. Healthy and diseased women should be comprehensively informed about their absolute individual risks for cancer, the benefits and harms of the surgery, alternative preventive strategies, and last but not least the competing risks of preceding carcinomas and cancer in general. Within the framework of non-directive counseling in the specialized centers of the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC), decision-making aids are being developed with grants from the Federal Ministry of Health and the German Cancer Aid to support women in making conclusive and satisfactory decisions.
      Breast Care 2014;9:385-389
  • Reproduction and Breast Cancer Risk
    • Abstract: Reproduction is doubtlessly one of the main biological meanings of life. It is therefore not surprising that various aspects of reproduction impact on breast cancer risk. Various developmental levels may become targets of breast tumorigenesis. This review follows the chronologic sequence of events in the life of a female at risk, starting with the intrauterine development. Furthermore, the influence of both contraceptive measures and fertility treatment on breast cancer development is dealt with, as well as various pregnancy-associated factors, events, and perinatal outcomes. Finally, the contribution of breast feeding to a reduced breast cancer risk is discussed.
      Breast Care 2014;9:398-405
  • Effect of Intravitreal Bevacizumab Injection before Ahmed Glaucoma Valve
           Implantation in Neovascular Glaucoma
    • Abstract: Ophthalmologica 2013;229:94–100
  • Long-Term Outcome of Polymyositis Treated with High Single-Dose
           Alternate-Day Prednisolone Therapy
    • Abstract: Eur Neurol 2012;68:117–121
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