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In all studies, the quality of cytology from self-sampling matched that of clinician-sampling. Women were generally positive about self-collection, but noted some concerns. CONCLUSION Self-sampling for HPV DNA testing seems to represent a feasible alternative to the Pap test. Further research is needed to provide a solid evidence base to inform using of self-sampling for HPV DNA testing for primary cervical cancer screening. © 2020 International Federation of Gynecology and Obstetrics.OBJECTIVE To evaluate the delivery-to-insertion interval for copper postpartum intrauterine devices (PPIUDs). https://www.selleckchem.com/products/aunp-12.html METHODS Secondary analysis of two related studies at five academic sites in India from March 2015 to July 2016. IUDs were inserted within 48 hours of vaginal delivery. Women (n=560) were grouped by whether they underwent postplacental (≤10 minutes) or immediate (>10 minutes) insertion. Outcomes were complete expulsion at the 6-8-week follow-up (primary), and IUD-to-fundus distance, as assessed by postinsertion ultrasound (secondary). RESULTS Overall, 93 (16.6%) women received a postplacental PPIUD and 467 (83.4%) received an immediate PPIUD. Complete expulsion at follow-up was 3.2% (n=3) in the postplacental and 7.5% (n=35) in the immediate postpartum group (P=0.176; difference in proportions, 4.3%; 95% confidence interval, -2.0 to 8.1). Distance from the fundus did not differ between the two groups (P=0.107); high fundal placement (≤10 mm from the internal endometrial verge) was achieved for most women. CONCLUSION The present data challenge previous guidance on the timing of PPIUD insertion. The 10-minute insertion window is a barrier to uptake and should be reassessed for inclusion in service delivery guidelines. A flexible interval would accommodate the multiple post-delivery tasks of providers and increase access to PPIUD. © 2020 International Federation of Gynecology and Obstetrics.Colibactin-producing E. coli (CoPEC) are frequently detected in colorectal cancer (CRC) and exhibit procarcinogenic properties. Because increasing evidence show the role of immune environment and especially of antitumor T-cells in CRC development, we investigated the impact of CoPEC on these cells in human CRC and in the APCMin/+ mice colon. T-cell density was evaluated by immunohistochemistry in human tumors known for their CoPEC status. APCmin/+ mice were chronically infected with a CoPEC strain (11G5). Immune cells (neutrophils and T-cell populations) were then quantified by immunofluorescent staining of the colon. The quantification of lymphoid populations was also performed in the mesenteric lymph nodes (MLNs). Here, we show that the colonization of CRC patients by CoPEC is associated with a decrease of tumor-infiltrating T lymphocytes (CD3+ T-cells). Similarly, we demonstrated, in mice, that CoPEC chronic infection decreases CD3+ and CD8+ T-cells and increases colonic inflammation. In addition, we noticed a significant decrease in antitumor T-cells in the MLNs of CoPEC-infected mice compared to that of controls. Moreover, we show that CoPEC infection decreases the antimouse PD-1 immunotherapy efficacy in MC38 tumor model. Our findings suggest that CoPEC could promote a procarcinogenic immune environment through impairment of antitumor T-cell response, leading to tumoral resistance to immunotherapy. CoPEC could thus be a new biomarker predicting the anti-PD-1 response in CRC. © 2020 UICC.Ovarian cancer is the most fatal gynecologic malignancy (50% 5-year survival) due to a typically advanced stage at diagnosis and a high rate of recurrence. Chemoprevention options are limited, and few interventions have been shown to reduce cancer risk or mortality. Emerging data support the model that fallopian tubes are the site of origin for a proportion of high-grade serous cancers. This implies that a subset of cancers may be prevented by removing the fallopian tubes while leaving the ovaries intact. Accordingly, there has been shift in clinical practice for average risk women; some now recommend removal of both the fallopian tubes only instead of tubal ligation for sterilization or at the time of benign gynecologic surgery. This has been termed opportunistic salpingectomy and represents a means of decreasing the burden of ovarian cancer by preventing cancers that arise in the fallopian tubes. There have been no detailed, prospective reports that have estimated ovarian cancer risk reduction with opportunistic salpingectomy, neither among women at baseline population risk nor among women at a high risk of developing the disease. The situation is complicated for women with a BRCA mutation-bilateral salpingo-oophorectomy is a proven means of risk reduction and salpingectomy alone is not the standard of care. Based on the existing data, salpingectomy alone should only be reserved for women with a lifetime risk of ovarian cancer of less than 5%. © 2020 UICC.Erythropoiesis-stimulating agents (ESAs) are available to treat chemotherapy-induced anemia (CIA). In 2007-2008, regulatory notifications advised of venous thromboembolism and mortality risks while the Center for Medicare and Medicaid Services' restricted ESA initiation to patients with hemoglobin less then 10 g/dl. In 2010, a Risk Evaluation and Mitigation Strategies required consent prior to administration. We evaluated ESA utilization from 2003 to 2012 and obtained private health insurer claims data for persons with lung, colorectal, or breast cancer from 2001 to 2012. ESA use for CIA was determined by an ESA claim after chemotherapy, up to 6 months after treatment. We identified 839,948 commercially insured patients, including 24,785 patients with ESA-treated CIA (3.2%). Darbepoetin use increased 3.9-fold from 2003 to 2007 (12.3% to 48.7%) and then decreased 95% to 2.6% by 2012. Epoetin use decreased 90% from 2003 to 2012 (30.3% to 3.1%). Between 2003 and 2012, mean epoetin dosing decreased 0.8-fold (244,979 in 2003 vs. 196,216 units in 2012), but increased 1.8-fold for darbepoetin-treated CIA (262 in 2003 to 467 μg in 2012). Among CIA patients, transfusions were low (4.5%) in 2002-2007, then increased 2.2-fold between 2008 and 2012. Safety initiatives between 2007 and 2010 facilitated reductions in ESA use combined with changes in coverage. These data show the efficacy of regulatory efforts, publication of adverse events and changes in reimbursement in reducing use of ESAs. Future studies are warranted to optimize deimplementation strategies to improve patient safety. © 2020 UICC.Effective analgesic alternatives to interscalene brachial plexus block are sought for shoulder surgery. Peri-articular infiltration analgesia is a novel, less invasive technique, but evidence surrounding its use is unclear. This systematic review and meta-analysis aims to evaluate the utility of peri-articular infiltration analgesia in shoulder surgery. We searched literature for trials comparing peri-articular infiltration analgesia with control or with interscalene brachial plexus block. Control groups received no intervention, placebo or systemic opioids. The primary outcome was cumulative oral morphine equivalent consumption during the first 24 h postoperatively. Secondary outcomes included rest pain scores up to 48 h; risk of side-effects; and durations of post-anaesthetic care unit and hospital stay. Data were pooled with random-effects modelling. Seven trials (383 patients) were included. Compared with control, peri-articular infiltration analgesia reduced 24-h oral morphine consumption by a mean difference (95%CI) of -38.0 mg (-65.5 to -10.5; p = 0.007). It also improved pain scores up to 6 h, 36 h and 48 h, with the greatest improvement observed at 0 h (-2.4 (-2.7 to -1.6); p less then 0.001). Peri-articular infiltration analgesia decreased postoperative nausea and vomiting by an odds ratio (95%CI) of 0.3 (0.1-0.7; p = 0.006). In contrast, peri-articular infiltration analgesia was not different from interscalene brachial plexus block for analgesic consumption, pain scores or side-effects. This review provides moderate evidence supporting peri-articular infiltration for postoperative analgesia following shoulder surgery. The absence of difference between peri-articular infiltration analgesia and interscalene brachial plexus block for analgesic outcomes suggests that these interventions are comparable, but further trials are needed to support this conclusion and identify the optimal peri-articular infiltration technique. © 2020 Association of Anaesthetists.BACKGROUND Human papillomavirus (HPV)-related disease remains a significant source of morbidity and mortality, and this underscores the need to increase HPV vaccination to reduce the burden of the disease. The objective of this study was to examine the association between the number of HPV vaccine doses and the risk of histologically confirmed preinvasive cervical disease and high-grade cytology. METHODS This retrospective matched cohort study used administrative data from Optum's Clinformatics DataMart Database to identify females aged 9 to 26 years who received 1 or more quadrivalent HPV vaccine doses between January 2006 and June 2015. Cases and controls were matched on region, age, sexually transmitted disease history, and pregnancy. All had a Papanicolaou test ≥1 year after the date of the matched case's final dose. Cox proportional hazards models were used to examine the association between the number of HPV vaccine doses and the incidence of preinvasive cervical disease and high-grade cytology. The Kaplan-Meier method was used to estimate the cumulative incidence rate at the 5-year follow-up. RESULTS The study included 133,082 females (66,541 vaccinated and 66,541 unvaccinated) stratified by the number of HPV vaccine doses and the vaccine initiation age. Among those aged 15 to 19 years, the hazard ratio (HR) for high-grade cytology for the 3-dose group was 0.84 (95% confidence interval [CI], 0.73-0.97), whereas the HRs for histologically confirmed preinvasive cervical disease for 1, 2, and 3 doses were 0.64 (95% CI, 0.47-0.88), 0.72 (95% CI, 0.54-0.95), and 0.66 (95% CI, 0.55-0.80), respectively. CONCLUSIONS The receipt of 1, 2, or 3 doses of an HPV vaccine by females aged 15 to 19 years was associated with a lower incidence of preinvasive cervical disease in comparison with unvaccinated females, and this supports the use of any HPV vaccination in reducing the burden of the disease. © 2020 American Cancer Society.The serine synthesis pathway (SSP) is active in multiple cancers. Previous study has shown that bortezomib (BTZ) resistance is associated with an increase in the SSP in multiple myeloma (MM) cells; however, the underlying mechanisms of SSP-induced BTZ resistance remain unclear. In this study, we found that phosphoglycerate dehydrogenase (PHGDH), the first rate-limiting enzyme in the SSP, was significantly elevated in CD138+ cells derived from patients with relapsed MM. Moreover, high PHGDH conferred inferior survival in MM. We also found that overexpression of PHDGH in MM cells led to increased cell growth, tumour formation, and resistance to BTZ in vitro and in vivo, while inhibition of PHGDH by short hairpin RNA or NCT-503, a specific inhibitor of PHGDH, inhibited cell growth and BTZ resistance in MM cells. Subsequent mechanistic studies demonstrated PHGDH decreased reactive oxygen species (ROS) through increasing reduced glutathione (GSH) synthesis, thereby promoting cell growth and BTZ resistance in MM cells.
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