Incidence and Risk Factors of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma Patients Having Undergone Autologous Stem Cell Transplantation

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe complication of bisphosphonate therapy. Due to their long survival and subsequently high cumulative doses of bisphosphonates, multiple myeloma patients have the highest risk of developing BRONJ of all patients treated with bisphosphonates. The purpose of the present study was to evaluate the incidence and risk factors for BRONJ in multiple myeloma patients after high-dose chemotherapy and autologous stem cell transplantation (ASCT). Patients and Methods: We retrospectively analyzed the data of 120 multiple myeloma patients after high-dose chemotherapy and ASCT treated with bisphosphonates and assessed the incidence and risk factors of BRONJ. Results: Of the 120 patients, 23 (19%) developed BRONJ. 6 patients suffered several BRONJ events, resulting in a total incidence of 23%. The risk for BRONJ was significantly higher for patients with rheumatism and recent dental manipulations. Furthermore, the number of previous bisphosphonate rotations, the duration of bisphosphonate therapy, and the type and cumulative dose of bisphosphonate used were associated with the incidence of BRONJ. Conclusion: Our study is the first to determine the risk of BRONJ in a homogeneous group of multiple myeloma patients treated with high-dose chemotherapy and ASCT

Buchbesprechungen aus Botanik und Naturschutz in Hessen Bd. 24

Es werden folgende Publikationen rezensiert: Chytrý: Vegetation of the Czech Republic 1, Chytrý: Vegetation of the Czech Republic 2, Chytrý: Vegetation of the Czech Republic 3, Eger & Kesper: Flechten zwischen Eder und Diemel, Gerster: Kräuterwissen, Meyer: Pflanzen Nordhessens, Mollenhauer: Gregor Kraus, Seibold: Schmeil-Fitschen, Suck & Bushart: Karte der Potentiellen Natürlichen Vegetation Deutschlands, Süß & al.: Ried und Sand

Expanding the Health Information National Trends Survey Research Program Internationally to Examine Global Health Communication Trends: Comparing Health Information Seeking Behaviors in the U.S. and Germany

The Health Information National Trends Survey (HINTS) is a well-established U.S.-based research program administered by the National Cancer Institute to track the public access to and use of health information. This paper introduces a German research initiative, part of the International Studies to Investigate Global Health Information Trends (INSIGHTS) research consortium. This adaptation of the HINTS is important for initiating analyses of global health communication practices and comparing health information seeking behaviors (HISB) across nations to pinpoint potentials and challenges of health information provision and contribute to a deeper understanding of socio-contextual determinants of HISB. First cross-country comparisons revealed that the share of residents seeking for health information is high in the U.S. (80%) and Germany (74%), but different primary sources are used. Whereas a clear majority of U.S. residents chose the Internet to gather health information (74.9%), Germans most often turn to health professionals (48.0%). Socio-structural and health(care)-related predictors were found to contribute to the explanation of HISB in both countries, whereas information-related predictors were only relevant in Germany. The results indicate the need to engage in patient-provider communication to initiate HISB and to improve the access to information for residents with lower socio-economic backgrounds

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

The mammalian target of rapamycin plays an important role in multiple myeloma. The allosteric mammalian target of rapamycin inhibitor everolimus has long been approved for immunosuppression and has shown activity in certain cancers. This investigator-initiated phase I trial explored the use of everolimus in relapsed and/or refractory multiple myeloma patients who had received two or more lines of prior treatment. Following a dose-escalation design, it called for a fixed dose of oral everolimus. Blood drug levels were monitored and the biological activity of everolimus was evaluated in bone marrow. Seventeen patients were enrolled (age range, 52 to 76 years). All had been previously treated with stem cell transplantation and proteasome inhibitors and almost all with immunomodulatory drugs. No dose-limiting toxicity was observed and the intended final daily dose of 10 mg was reached. Only one severe adverse event was assessed as possibly related to the study drug, namely atypical pneumonia. Remarkably few infections were observed. Although the trial was mainly designed to evaluate feasibility, anti-myeloma activity, defined as clinical benefit, was documented in ten of 15 evaluable patients at every dose level including eight patients with stable disease, one patient with minor remission and one with partial remission. However, the median time to progression was 90 days (range, 13 to 278 days). The biomarker study documented on-target activity of everolimus in malignant plasma cells as well as the microenvironment. The observed responses are promising and allow further studies to be considered, including those testing combination strategies addressing escape pathways

Activity of everolimus (RAD001) in relapsed and/or refractory multiple myeloma: a phase I study

The mammalian target of rapamycin plays an important role in multiple myeloma. The allosteric mammalian target of rapamycin inhibitor everolimus has long been approved for immunosuppression and has shown activity in certain cancers. This investigator-initiated phase I trial explored the use of everolimus in relapsed and/or refractory multiple myeloma patients who had received two or more lines of prior treatment. Following a dose-escalation design, it called for a fixed dose of oral everolimus. Blood drug levels were monitored and the biological activity of everolimus was evaluated in bone marrow. Seventeen patients were enrolled (age range, 52 to 76 years). All had been previously treated with stem cell transplantation and proteasome inhibitors and almost all with immunomodulatory drugs. No dose-limiting toxicity was observed and the intended final daily dose of 10 mg was reached. Only one severe adverse event was assessed as possibly related to the study drug, namely atypical pneumonia. Remarkably few infections were observed. Although the trial was mainly designed to evaluate feasibility, anti-myeloma activity, defined as clinical benefit, was documented in ten of 15 evaluable patients at every dose level including eight patients with stable disease, one patient with minor remission and one with partial remission. However, the median time to progression was 90 days (range, 13 to 278 days). The biomarker study documented on-target activity of everolimus in malignant plasma cells as well as the microenvironment. The observed responses are promising and allow further studies to be considered, including those testing combination strategies addressing escape pathways

Evaluation of hypochlorous acid as an ear flush in dogs with chronic otitis externa

BackgroundChronic otitis externa (OE) in dogs frequently requires anaesthetised ear flushing. ObjectivesTo evaluate hypochlorous acid as an ear flushing and antimicrobial agent in dogs with chronic OE. AnimalsTwenty dogs with chronic OE caused by the same organisms bilaterally. Materials and MethodsOne ear was flushed under anaesthesia with hypochlorous acid, the other with saline solution. Subsequently, the ear flushed with hypochlorous acid was cleaned with the same solution twice daily for 2 weeks, the other ear with a commercial ear cleaner. An ear medication containing miconazole, polymyxin B and prednisolone was used once daily in both ears. Clinical scores were determined before the flush. Ear cytological results were obtained, a hearing test was conducted before and after the ear flush, and a culture was taken directly after flushing. Ears were evaluated after 2 weeks of therapy. ResultsYeast was present in the ears of 11, cocci in one and a mixed infection in eight dogs. Five ears were negative on culture after flushing with hypochlorous acid, one after the saline flush. Clinical and cytological scores decreased significantly with both solutions after 2 weeks of treatment. There was no difference between treatments in any of the scores at any time point between treatments and in the results of the hearing test before and after the flushing procedure. Adverse effects were not seen. Conclusions and Clinical RelevanceHypochlorous acid is a suitable cleaning solution for canine OE

Expanding the Genetic Code of and to Incorporate Non-canonical Amino Acids for Production of Modified Lantibiotics

The incorporation of non-canonical amino acids (ncAAs) into ribosomally synthesized and post-translationally modified peptides, e.g., nisin from the Gram-positive bacterium Lactococcus lactis, bears great potential to expand the chemical space of various antimicrobials. The ncAA Nε-Boc-L-lysine (BocK) was chosen for incorporation into nisin using the archaeal pyrrolysyl-tRNA synthetase–tRNAPyl pair to establish orthogonal translation in L. lactis for read-through of in-frame amber stop codons. In parallel, recombinant nisin production and orthogonal translation were combined in Escherichia coli cells. Both organisms synthesized bioactive nisin(BocK) variants. Screening of a nisin amber codon library revealed suitable sites for ncAA incorporation and two variants displayed high antimicrobial activity. Orthogonal translation in E. coli and L. lactis presents a promising tool to create new-to-nature nisin derivatives

Aplastic Crisis as Primary Manifestation of Systemic Lupus Erythematosus

Aplastic crisis is an unusual feature of systemic lupus erythematosus (SLE). We report the case of a 54-year-old woman presenting with both (extravascular) Coombs-positive hemolytic anemia and laboratory findings of bone marrow hyporegeneration with concomitant severe neutropenia. A bone marrow biopsy confirmed aplastic crisis. Diagnostic work-up revealed soaring titers of autoantibodies (anti-nuclear, anti-double-stranded DNA, anti-cardiolipin-IgM, and anti-beta 2-glykoprotein-IgM antibodies), indicating a connective tissue disease as the most plausible reason for bone marrow insufficiency. As the criteria for SLE were fulfilled, we initiated an immunosuppressive therapy by steroids, which led to a rapid complete hematologic and clinical remission in our patient. In this case, we could report on one of the rare cases of SLE-induced aplastic crisis showing that this condition can be entirely reversed by immunosuppressive treatment and that SLE-induced aplastic crisis yields a good prognosis. In conclusion, in a case of aplastic crisis, physicians should be aware that SLE can be a rare cause that is accessible to specific treatment

A randomised, double-blinded comparison between subcutaneous rush and intralympathic allergen immunotherapy induction in atopic dogs

BackgroundAtopic dermatitis (AD) is one of the most common skin diseases in small animal practice. Allergen immunotherapy (AIT) is the only curative treatment for the disease, and oral, subcutaneous and intralymphatic administration of allergens are commonly employed. ObjectivesTo compare the efficacy of AIT following an induction phase with intralymphatic injections (ILIT) or rush immunotherapy (RIT). AnimalsFifty privately owned dogs with AD. Materials and MethodsIn a double-blinded study, dogs were randomly assigned to either four monthly ILIT of allergen extract or RIT with five injections administered subcutaneously at hourly intervals on the first day. They were assessed by validated scores;Canine Atopic Dermatitis Lesion Index (CADLI) and pruritus Visual Analog Scale (PVAS) at the beginning of the study and after 1, 3, 6 and 12 months. The latter were performed daily for 7 days before each revisit. Medication scores and a total clinical score were calculated and compared between each group and time point. ResultsThere was no significant difference in CADLI and PVAS scores, or CADLI and medication scores between groups at any of the time points. A significant improvement with both ILIT and RIT was seen in total and pruritus scores, respectively. An owner global assessment of good-to-excellent treatment efficacy was seen in 40% of the dogs;total scores improved by 27% and 35% in the RIT and ILIT group, respectively. Adverse effects were not seen. Conclusions and Clinical RelevanceInduction of AIT can be conducted either as RIT or ILIT with no loss in efficacy

Identification of extremely GC-rich micro RNAs for RT-qPCR data normalization in human plasma

We aimed at extending the repertoire of high-quality miRNA normalizers for reverse transcription-quantitative PCR (RT-qPCR) of human plasma with special emphasis on the extremely guanine-cytosine-rich portion of the miRNome. For high-throughput selection of stable candidates, microarray technology was preferred over small-RNA sequencing (sRNA-seq) since the latter underrepresented miRNAs with a guanine-cytosine (GC) content of at least 75% (p = 0.0002, n = 2). miRNA abundances measured on the microarray were ranked for consistency and uniformity using nine normalization approaches. The eleven most stable sequences included miRNAs of moderate, but also extreme GC content (45%–65%: miR-320d, miR-425-5p, miR-185-5p, miR-486-5p; 80%–95%: miR-1915-3p, miR-3656-5p, miR-3665-5p, miR-3960-5p, miR-4488-5p, miR-4497 and miR-4787-5p). In contrast, the seven extremely GC-rich miRNAs were not found in the two plasma miRNomes screened by sRNA-seq. Stem-loop RT-qPCR was employed for stability verification in 32 plasma samples of healthy male Caucasians (age range: 18–55 years). The lowest inter-individual variance of miRNA abundance was determined for miR-3665 and miR-1915-3p [coefficient of variation (CV) values: 0.08 and 0.50, respectively]. The eight most stable sequences included four extremely GC-rich miRNAs (miR-1915-3p, miR-3665, miR-4787-5p and miR-4497). The best-performing duo normalization factor (NF) for the condition of human plasma, miR-320d and miR-4787-5p, also included a GC-extreme miRNA. In summary, the identification of extremely guanine-cytosine-rich plasma normalizers will help to increase accuracy of PCR-based miRNA quantification, thus raise the potential that miRNAs become markers for psychological stress reactions or early and precise diagnosis of clinical phenotypes. The novel miRNAs might also be useful for orthologous contexts considering their conservation in related animal genomes