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Molecular diagnostics of inherited platelet disorders (IPD) has been revolutionized by the implementation of high-throughput sequencing (HTS) approaches. A conclusive diagnosis using HTS tests can be obtained quickly and cost-effectively in many, but not all patients. The expanding use of HTS tests has raised concerns regarding complex variant interpretation and the ethical implications of detecting unsolicited findings such as variants in IPD genes RUNX1, ETV6, and ANKRD26, which are associated with increased leukemic risk. This guidance document has been developed and written by a multidisciplinary team of researchers and clinicians, with expertise in hematology, clinical and molecular genetics, and bioethics, alongside a RUNX1 patient advocacy representative. We recommend that for clinical diagnostics, HTS for IPD should use a multigene panel of curated diagnostic-grade genes. Critically, we advise that an HTS test for clinical diagnostics should only be ordered by a clinical expert that is (a) fully aware of the complexity of genotype-phenotype correlations for IPD; (b) able to discuss these complexities with a patient and family members before the test is initiated; and (c) able to interpret and appropriately communicate the results of a HTS diagnostic report, including the implication of variants of uncertain clinical significance. Each patient should know what an HTS test could mean for his or her clinical management before initiating a test. We hereby propose an exemplified informed consent document that includes information on these ethical concerns and can be used by the community for implementation of HTS of IPD in a clinical diagnostic setting. This paper does not include recommendations for HTS of IPD in a research setting.Yersinia pseudotuberculosis has been studied for many decades, and research on this microbe has taught us a great deal about host-pathogen interactions, bacterial manipulation of host cells, virulence factors, and the evolution of pathogens. This microbe should not be cultivated at 37°C because this is a trigger that the bacterium uses to sense its presence within a mammalian host and results in expression of genes necessary to colonize a mammalian host. Prolonged growth at this temperature can result in accumulation of mutations that reduce the virulence of the strain, so all protocols need to be modified for growth at room temperature, or 26°C. This article describes protocols for cultivating this microbe and for its long-term storage and its genetic manipulation by transformation and conjugation. © 2020 Wiley Periodicals LLC. Basic Protocol 1 Growth of Y. pseudotuberculosis from a stock Basic Protocol 2 Growth of Y. pseudotuberculosis in liquid medium from a single colony Basic Protocol 3 Freezing Y. pseudotuberculosis in glycerol for long-term storage Basic Protocol 4 Transformation of Y. pseudotuberculosis by electroporation Basic Protocol 5 Tri-parental mating/conjugation.The current TNM staging system uses the same category definitions for both rectal cancer patients with and without neoadjuvant chemoradiotherapy (NCRT). However, ypTNM stage, especially ypN stage does not predict patient survival after NCRT well. Whether tumor regression in lymph nodes (LRG) may improve the prediction has not been well studied. In total, 358 patients with rectal cancer who received NCRT followed by radical resection were recruited from 2004 to 2015, and the median follow-up time was 57.5 months. The main outcome measure was disease-free survival (DFS). In univariate analysis, factors associated with DFS were ypT stage, ypN stage, number of negative lymph nodes (NLN), lymph node ratio (LNR), tumor regression grade (TRG), M-TTRG (modified ypT stage by combining ypT stage and TRG), maximum LRG (LRGmax), sum score of LRG (LRGsum), LRG ratio (average value of LRGsum), and M-NLRG (modified ypN stage by combining LRGmax and LNR). In the multivariate Cox regression analysis, M-TTRG and M-NLRG (p less then 0.001 and p = 0.030, respectively) were significantly associated with DFS. The estimated 5-year DFS rates were 86.6%, 60.3%, and 36.4% for patients with M-NLRG-0, M-NLRG-1, and M-NLRG-2, respectively (p less then 0.001). A significant difference in survival was observed among patients with NCRT after incorporating TRG and LRG simultaneously into the current ypTNM staging system (p less then 0.001). LRG was an important prognostic factor in rectal cancer patients treated with NCRT and could refine the ypTNM staging system. The modified ypTNM staging system in combination with LRGmax, LNR, and TRG could improve the DFS prediction in each subset of patients.
To review the clinical use and the effectiveness of tamoxifen in patients with advanced or recurrent ovarian cancer.
A retrospective review of clinical records was conducted in patients who received tamoxifen for the treatment of ovarian cancer between 2002 and 2016. We reviewed the clinical setting that it was given, duration of use, patients' tolerability, clinical benefit and progression-free survival. We also attempted to identify predictive markers for response.
A total of 92 patients received tamoxifen during this 15-year period. The patients received a median of 2.5 lines of chemotherapy before switching to tamoxifen, and they remained on tamoxifen for a median of 5.6 months (range 0-85 months), with 24 patients receiving it for more than 12 months. Seventy-six patients continued on tamoxifen for more than 2 months. INDY inhibitor datasheet In this group, 75 patients had an evaluable response, either by CA 125 or clinically and clinical benefit rate (defined as complete, partial response and static disease) was seen in 42 patients (56%), with majority of patients having static disease. The median progression-free survival was 5.3 months (95% confidence interval, 2.6-8.1). Tamoxifen was well tolerated. Hormone receptor status was not demonstrated to predict response.
Patients with advanced ovarian cancer who have failed previous lines of chemotherapy may achieve static disease with tamoxifen with minimal side effects. Tamoxifen may still have a role in the era of molecular target therapy.
Patients with advanced ovarian cancer who have failed previous lines of chemotherapy may achieve static disease with tamoxifen with minimal side effects. Tamoxifen may still have a role in the era of molecular target therapy.