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91.
Pancreatic ductal adenocarcinoma (PDAC) is predicted to become the second leading cause of cancer-related mortality within the next decade, with limited effective treatment options and a dismal long-term prognosis for patients. Genomic profiling has not yet manifested clinical benefits for diagnosis, treatment or prognosis in PDAC, due to the lack of available tissues for sequencing and the confounding effects of low tumour cellularity in many biopsy specimens. Increasing focus is now turning to the use of minimally invasive liquid biopsies to enhance the characterisation of actionable PDAC tumour genomes. Circulating tumour DNA (ctDNA) is the most comprehensively studied liquid biopsy analyte in blood and can provide insight into the molecular profile and biological characteristics of individual PDAC tumours, in real-time and in advance of traditional imaging modalities. This can pave the way for identification of new therapeutic targets, novel risk variants and markers of tumour response, to supplement diagnostic screening and provide enhanced scrutiny in treatment stratification. In the roadmap towards the application of precision medicine for clinical management in PDAC, ctDNA analyses may serve a leading role in streamlining candidate biomarkers for clinical integration. In this review, we highlight recent developments in the use of ctDNA-based liquid biopsies for PDAC and provide new insights into the technical, analytical and biological challenges that must be overcome for this potential to be realised. 相似文献
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Qiaojie Wang Karan Goswami Noam Shohat Arash Aalirezaie Jorge Manrique Javad Parvizi 《The Journal of arthroplasty》2019,34(5):947-953
Background
Whether prolonged operative time is an independent risk factor for subsequent surgical site infection (SSI) and periprosthetic joint infection (PJI) following total joint arthroplasty (TJA) remains a clinically significant and underexplored issue. The aim of this study is to investigate the association between operative time and the risk of subsequent SSI and PJI in patients undergoing primary TJA.Methods
We retrospectively reviewed 17,342 primary unilateral total knee arthroplasty and total hip arthroplasty performed at a single institution between 2005 and 2016, with a minimum follow-up of 1 year. A multivariate logistic regression model was conducted to identify the association between operative time and the development of SSI within 90 days and PJI within 1 year.Results
Overall, the incidence of 90-day SSI and 1-year PJI was 1.2% and 0.8%, respectively. Patients with an operative time of >90 minutes had a significantly higher incidence of SSI and PJI (2.1% and 1.4%, respectively) compared to cases lasting between 60 and 90 minutes (1.1% and 0.7%), and those lasting ≤60 minutes (0.9% and 0.7%, P < .01). In the multivariate model, the risk for infection increased by an odds ratio of 1.346 (95% confidential interval 1.114-1.627) for 90-day SSI and 1.253 (95% confidential interval 1.060-1.481) for 1-year PJI for each 20-minute increase in operative time.Conclusion
In patients undergoing primary TJA, each 20-minute increase in operative time was associated with nearly a 25% increased risk of subsequent PJI. We advocate that surgeons pay close attention to this underappreciated risk factor while maintaining safe operative practices, which minimize unnecessary steps and wasted time in the operating room. 相似文献93.
Dana Franzen-Klein Mark Jankowski Charlotte L. Roy Hoa Nguyen-Phuc Da Chen Lorin Neuman-Lee 《Journal of toxicology and environmental health. Part A》2020,83(2):45-65
ABSTRACTDomestic chickens (Gallus gallus domesticus) were exposed to imidacloprid by gavage once daily for 7 consecutive days at 0, 0.03, 0.34, 3.42, 10.25, and 15.5 mg/kg/day (n = 20 per group; 5 6-week-old males, 5 6-week-old females, 5 9-week-old males, and 5 9-week-old females). The severity and duration of neurobehavioral abnormalities were recorded. Components of the innate and adaptive immune system were assessed with 7 standard functional assays. Temporary neurobehavioral abnormalities were observed in a dose-dependent manner, including muscle tremors, ataxia, and depressed mentation. Based upon mean clinical severity scores, the no observed adverse effect level (NOAEL) was 3.42 mg/kg/day, and the lowest observed adverse effect level (LOAEL) was 10.25 mg/kg/day. The effective dose value for the presence of any neurobehavioral abnormalities in 50% of the test group (ED50) was 4.62 ± 0.98 mg/kg/day. The ED50 for an adjusted score that included both severity and duration of neurobehavioral abnormalities was 11.24 ± 9.33 mg/kg/day. These ED50 values are equivalent to a 1 kg bird ingesting 29 or 70 imidacloprid treated soybean seeds respectively. Immunotoxicity was not documented, possible causes include the assays were insensitive, relevant immune functions were not examined, or imidacloprid is not immunotoxic at this dosing schedule in this species. Neurobehavioral abnormalities were a more sensitive indicator of the sublethal effects of imidacloprid than immunotoxicity. 相似文献
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Eric S. Zhou Larissa Nekhlyudov Sharon L. Bober 《Translational andrology and urology》2015,4(2):218-231
There is a large and growing population of long-term cancer survivors. Primary care physicians (PCPs) are playing an increasingly greater role in the care of these patients across the continuum of cancer survivorship. In this role, PCPs are faced with the responsibility of managing a range of medical and psychosocial late effects of cancer treatment. In particular, the sexual side effects of treatment which are common and have significant impact on quality of life for the cancer survivor, often go unaddressed. This is an area of clinical care and research that has received increasing attention, highlighted by the presentation of this special issue on Cancer and Sexual Health. The aims of this review are 3-fold. First, we seek to overview common presentations of sexual dysfunction related to major cancer diagnoses in order to give the PCP a sense of the medical issues that the survivor may present with. Barriers to communication about sexual health issues between patient/PCPs in order are also described in order to emphasize the importance of PCPs initiating this important conversation. Next, we provide strategies and resources to help guide the PCP in the management of sexual dysfunction in cancer survivors. Finally, we discuss case examples of survivorship sexual health issues and highlight the role that a PCP can play in each of these case examples. 相似文献
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