Oude Ophuis C.M.C.,Netherlands Cancer Institute |
Verhoef C.,Netherlands Cancer Institute |
Rutkowski P.,Center of Oncology of Poland |
Powell B.W.E.M.,St George's, University of London |
And 9 more authors.
European Journal of Surgical Oncology | Year: 2016
Background: Worldwide, sentinel node biopsy (SNB) is the recommended staging procedure for stage I/II melanoma. Most melanoma guidelines recommend re-excision plus SNB as soon as possible after primary excision. To date, there is no evidence to support this timeframe. Aim: To determine melanoma specific survival (MSS) for time intervals between excisional biopsy and SNB in SNB positive patients. Methods: Between 1993 and 2008, 1080 patients were diagnosed with a positive SNB in nine Melanoma Group centers. We selected 1015 patients (94%) with known excisional biopsy date. Time interval was calculated from primary excision until SNB. Kaplan-Meier estimated MSS was calculated for different cutoff values. Multivariable analysis was performed to correct for known prognostic factors. Results: Median age was 51 years (Inter Quartile Range (IQR) 40-62 years), 535 (53%) were men, 603 (59%) primary tumors were located on extremities. Median Breslow thickness was 3.00 mm (IQR 1.90-4.80 mm), 442 (44%) were ulcerated. Median follow-up was 36 months (IQR 20-62 months). Median time interval was 47 days (IQR 32-63 days). Median Breslow thickness was equal for both <47 days and ≥47 days interval: 3.00 mm (1.90-5.00 mm) vs 3.00 mm (1.90-4.43 mm) (p = 0.402). Sentinel node tumor burden was significantly higher in patients operated ≥47 days (p = 0.005). Univariate survival was not significantly different for median time interval. Multivariable analysis confirmed that time interval was no independent prognostic factor for MSS. Conclusions: Time interval from primary melanoma excision until SNB was no prognostic factor for MSS in this SNB positive cohort. This information can be used to counsel patients. © 2016.
PubMed | Netherlands Cancer Institute, Italian National Cancer Institute, St George's, University of London, University of Groningen and 4 more.
Type: Journal Article | Journal: European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology | Year: 2016
Worldwide, sentinel node biopsy (SNB) is the recommended staging procedure for stage I/II melanoma. Most melanoma guidelines recommend re-excision plus SNB as soon as possible after primary excision. To date, there is no evidence to support this timeframe.To determine melanoma specific survival (MSS) for time intervals between excisional biopsy and SNB in SNB positive patients.Between 1993 and 2008, 1080 patients were diagnosed with a positive SNB in nine Melanoma Group centers. We selected 1015 patients (94%) with known excisional biopsy date. Time interval was calculated from primary excision until SNB. Kaplan-Meier estimated MSS was calculated for different cutoff values. Multivariable analysis was performed to correct for known prognostic factors.Median age was 51 years (Inter Quartile Range (IQR) 40-62 years), 535 (53%) were men, 603 (59%) primary tumors were located on extremities. Median Breslow thickness was 3.00mm (IQR 1.90-4.80mm), 442 (44%) were ulcerated. Median follow-up was 36 months (IQR 20-62 months). Median time interval was 47 days (IQR 32-63 days). Median Breslow thickness was equal for both <47 days and 47 days interval: 3.00mm (1.90-5.00mm) vs 3.00mm (1.90-4.43mm) (p=0.402). Sentinel node tumor burden was significantly higher in patients operated 47 days (p=0.005). Univariate survival was not significantly different for median time interval. Multivariable analysis confirmed that time interval was no independent prognostic factor for MSS.Time interval from primary melanoma excision until SNB was no prognostic factor for MSS in this SNB positive cohort. This information can be used to counsel patients.
Tiburzy B.,University of Lübeck |
Kulkarni U.,University of Lübeck |
Hauser A.E.,University of Medicine Berlin |
Abram M.,University of Marburg |
Manz R.A.,University of Lübeck
Seminars in Immunopathology | Year: 2014
Plasma cells are terminally differentiated B cells that secrete antibodies, important for immune protection, but also contribute to any allergic and autoimmune disease. There is increasing evidence that plasma cell populations exhibit a considerable degree of heterogeneity with respect to their immunophenotype, migration behavior, lifetime, and susceptibility to immunosuppressive drugs. Pathogenic long-lived plasma cells are refractory to existing therapies. In contrast, short-lived plasma cells can be depleted by steroids and cytostatic drugs. Therefore, long-lived plasma cells are responsible for therapy-resistant autoantibodies and resemble a challenge for the therapy of antibody-mediated autoimmune diseases. Both lifetime and therapy resistance of plasma cells are supported by factors produced within their microenviromental niches. Current results suggest that plasma cell differentiation and survival factors such as IL-6 also signal via mammalian miRNAs within the plasma cell to modulate downstream transcription factors. Recent evidence also suggests that plasma cells and/or their immediate precursors (plasmablasts) can produce important cytokines and act as antigen-presenting cells, exhibiting so far underestimated roles in immune regulation and bone homeostasis. Here, we provide an overview on plasma cell biology and discuss exciting, experimental, and potential therapeutic approaches to eliminate pathogenic plasma cells. © 2014 Springer-Verlag.
Tang L.Y.,Chinese University of Hong Kong |
Li L.,Chinese University of Hong Kong |
Borchert A.,University of Medicine Berlin |
Lau C.B.S.,Chinese University of Hong Kong |
And 2 more authors.
Molecular Human Reproduction | Year: 2012
Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese herbal medicine for threatened miscarriage. Potential reproductive toxicity of LAR was identified in early pregnancy in animals. Skeletal anomalies including loss of ulna and distal digits, shortening of humerus and radius were observed in higher clinical dose groups. Here, we aimed to study the molecular mechanism of the congenital malformation induced by LAR. In vitro whole mouse embryo culture was used to confirm the embryotoxicity effects of LAR on developing limb buds during early organogenesis. A pregnant mouse model was employed to study the developmental gene expression by quantitative PCR and whole hybridization and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, in the forelimbs and hindlimbs during development in vivo. Severe growth retardation, multiple embryonic malformations and delayed limb bud development were observed. Limb-specific Tbx gene expressions in both developing forelimbs and hindlimbs were significantly decreased. Increased developmental apoptosis in apical ectodermal ridge and mesenchymal mesoderm of the developing limb buds was identified. Overexpressions of Tbx2 and Tbx3 in embryos in vitro rescued LAR-induced abnormal limb development and reduced apoptosis in the developing forelimb buds. In conclusion, LAR affects limb development by suppressing the expression of limb developmental genes and disturbing programmed cell death during limb formation in mice. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Schmidt S.C.,University of Medicine Berlin |
Schumacher G.,University of Medicine Berlin |
Klage N.,Clinic for General and Visceral Surgery |
Chopra S.,University of Medicine Berlin |
And 2 more authors.
Surgical Endoscopy and Other Interventional Techniques | Year: 2010
Background: In recent years, laparoscopic hepatic resection is performed by an increasing number of surgeons. Despite many advantages of the laparoscopic procedure, it is unclear whether the pneumoperitoneum affects the postoperative liver regeneration after liver resection. The current study aimed to investigate the influence of a carbon dioxide (CO2) pneumoperitoneum on liver regeneration in a rat model. Methods: In this study, 60 male Wistar rats were subjected to 70% partial hepatic resection. Of these 60 animals, 30 underwent preoperative pneumoperitoneum at 9 mmHg for 60 min. After hepatic resection, the rats were killed at 12, 24, and 48 h, and on days 4 and 7. The outcome parameters were hepatocellular injury (plasma aminotransferases), oxidative stress (plasma malondialdehyde), interleukin-6 (IL-6), and liver regeneration (mitotic index, KI-67; regenerating liver mass). Results: The mitotic index was significantly lower in the pneumoperitoneum group than in the group without pneumoperitoneum at all time points (p < 0.05). In the pneumoperitoneum group, KI-67 was significantly lower on day 4 (p < 0.05). The liver regeneration rate was significantly lower for the animals with pneumoperitoneum on days 2 and 4 (p < 0.05). The postoperative hepatocellular injury was significantly greater after pneumoperitoneum at 12, 24, and 48 h (p < 0.05). Plasma malondialdehyde and IL-6 were significantly higher in the pneumoperitoneum group at 24 h and on day 4 (p < 0.05). Conclusion: This study showed that pneumoperitoneum before extended liver resection impaired postoperative liver regeneration. Oxidative stress reaction and hepatocellular damage was markedly higher after pneumoperitoneum. Further investigations, especially with patients that have impaired liver function, are necessary for clinical consequences to be drawn from these results. © 2009 Springer Science+Business Media, LLC.
Jacobs J.W.G.,University Utrecht |
Da Silva J.A.P.,University of Coimbra |
Armbrecht G.,University of Medicine Berlin |
Bijlsma J.W.J.,University Utrecht |
Verstappen S.M.M.,University Utrecht
Journal of Rheumatology | Year: 2010
Objective. To investigate basic assumptions of prediction models for future vertebral fractures. Methods. Lateral radiographs of the spine were obtained from 314 Portuguese individuals aged 60 years or older (205 women and 109 men) with bone mineral density (BMD) measurements at several sites. Associations between BMD at various sites, participant characteristics, and vertebral fractures were investigated. For men and women separately, logistic regression analyses and analyses of areas under the receiver-operating characteristic (ROC) curves were performed to determine the accuracy of BMD measurment at predicting the presence of vertebral deformities. Results. BMD measurements at all sites significantly predicted the presence of osteoporotic vertebral deformities in women but not in men. Similarly, in analyses of areas under ROC curves, BMD assessments were statistically significantly related to vertebral deformities in women but not in men. In multivariate analyses, BMD measurements of the lumbar spine and of the forearm, adjusted for gender, age, and body mass index, significantly predicted the presence of vertebral deformity, but BMD of the hip sites did not. Conclusion. Prediction of fractures is specific for gender and site of BMD measurement. This challenges the use of similar algorithms for men and women as well as the use of hip BMD data to accurately estimate future vertebral fracture risk. The Journal of Rheumatology Copyright © 2010. All rights reserved.
News Article | February 27, 2017
You may never have heard of Acinetobacter baumannii, Pseudomonas aeruginosa, or the Enterobacteriaceae—but these three killers top a new list, drawn up by the World Health Organization (WHO) in Geneva, Switzerland, of bacteria for which new drugs are desperately needed. Unveiled today, the list contains 12 bacteria and bacterial families, with the top three making up the category “critical.” The list “is not meant to scare people about new superbugs, but to signal to researchers and pharmaceutical companies what their priorities should be,” Marie-Paule Kieny, WHO’s assistant director-general for health systems and innovation, told a press conference today. The crucial drugs are unlikely to be big moneymakers for companies that develop them, she notes, so governments and health agencies need to cooperate to boost the chances that they will be developed in time. Doctors, researchers, and health officials have been sounding the alarm for years about the rise of antibiotic resistance. The list, developed by researchers at the University of Tübingen in Germany, took into account the level of resistance each class of pathogen has already acquired, how deadly it can be, how widespread, and the burden it causes to health systems. The top three are all gram-negative bacteria that are resistant to multiple drugs. They aren’t widespread yet, but they do cause severe, frequently deadly infections in hospitals, especially in people who are already immune compromised—including transplant recipients, chemotherapy patients, and elderly people. Just last month, for instance, a woman in Nevada died of an infection with a so-called CRE, or carbapenem-resistant Enterobacteriaceae. These bacteria can cause deadly infections if they take up residence in the respiratory system or bloodstream. The most dangerous strains have recently acquired resistance to a class of antibiotics called carbapenems, the only group that still killed them effectively. Nine more pathogens round out the agency’s dirty dozen: Six are listed as high priority, including drug-resistant strains of Neisseria gonorrhoeae, which causes gonorrhea, and food-borne agents like Salmonella and Campylobacter. Bacteria in this category cause infections that are less deadly than those caused by the three critical-level bugs, but they are much more widespread. Three “medium” priority organisms all are susceptible to some drugs, but are increasingly becoming resistant. The list “sets priorities in the right direction,” says Petra Gastmeier, head of the Institute for Hygiene and Environmental Medicine at Charité University of Medicine Berlin, who wasn’t involved in the development of the list. In the current market, antibiotics aren’t an attractive investment, Kieny says. When used properly, the drugs are taken only for a short time, so they don’t bring in the high returns that drugs for chronic diseases do. “And rather than trying to maximize sales, we need to restrict usage,” Kieny says, to delay the inevitable emergence of resistance. Part of the solution will be finding new ways to reward companies for developing antibiotics, Kieny says. One idea is to agree to pay companies a big up-front fee, or “prize” as soon as a new drug comes on the market, with guidelines in place so that it would be used sparingly. But governments or other donors would have to agree to pay for the prize money. One drug-resistant bacterial pathogen is notably absent from the list: Mycobacterium tuberculosis. The problem of drug-resistant tuberculosis (TB) is "already a globally established priority," the report says; the goal was to increase attention to threats not yet widely recognized. But the TB Alliance, a nonprofit research and advocacy group based in New York City, calls on WHO to reconsider. "The absence of TB from this list is shocking,” the alliance's President and CEO Mel Spigelman said in a statement yesterday. "Every global effort to address the burgeoning AMR [antimicrobial resistance] emergency must include TB." In a response , WHO Director-General Margaret Chan emphasized that "[a]ddressing drug-resistant TB research is a top priority for WHO and for the world." WHO released its list ahead of a meeting of G20 health experts this week in Berlin, where the topic of antibiotic resistance is high on the agenda. The focus is appropriate, Gastmeier says. “This is not a problem that we can solve at a national level, and it is one in which low- and middle-income countries are linked to high-income ones.” A prime example: The woman who died in Nevada had spent time in India, where she most likely acquired the resistant strain. *Update, 1 March, 10:35 a.m.: This item has been updated to include a statement from the TB Alliance and additional comments from WHO.