Klavsenleonard1661

The management of severe adverse events (AEs) is important in safely and effectively providing chemotherapy to older adults with diffuse large B-cell lymphoma (DLBCL). However, reports on simple and DLBCL-specific predictive models for treatment-related toxicity in elderly individuals are scarce. The aim of this study was to examine the usefulness of Geriatric 8 (G8) in predicting treatment-related severe AEs, nonhematological toxicity, and febrile neutropenia in older adults with DLBCL in real-world practice.

We conducted a multicenter, retrospective study on 398 consecutive patients with DLBCL (aged ≥65 years) who received standard therapy at three centers in Japan (University of Fukui Hospital, the Fukui Prefectural Hospital, and the Japanese Red Cross Fukui Hospital), between 2007 and 2017.

Multivariate logistic analysis demonstrated that the G8 score was an independent predictive factor for severe AEs. Moreover, a logistic regression model with restricted cubic spline showed a nonlinear associationo accurately predict the risk of severe adverse events (AEs) in advance is essential for safe and effective treatment. This study demonstrated that the Geriatric 8 score, a simple and established geriatric assessment tool, indicated a high predictive ability for occurrence of therapy-related severe AEs in elderly patients with DLBCL who were treated with standard treatment.Oral infection with human papillomavirus (HPV) is likely to underpin the rapidly rising incidence of oropharyngeal squamous cell carcinoma; however, there are few data describing the natural history of oral HPV infection. We recruited 704 participants aged 20 to 70 years from worksites, universities and primary care practices in Brisbane, Australia. Trichostatin A nmr Participants completed questionnaires at baseline, 12 and 24 months and donate four saliva samples at baseline, 6, 12 and 24 months for HPV polymerase chain reaction testing and typing. We estimated the prevalence of oral HPV infection at baseline, incidence of new infections among those HPV-negative at baseline, clearance rate and persistent infections. At baseline, 10.7% of participants had oral HPV infections from 26 different HPV types. Sexual behaviours were associated with oral HPV infection, including more partners for passionate kissing (29 or more; odds ratio [OR] 3.4, 95% confidence interval [CI] 1.5-8.0), and giving and receiving oral sex (16 or more; OR 5.4, 95% CI 1.6-17.7 and OR 5.6, 95% CI 1.6-18.7, respectively). Of 343 participants, HPV-free at baseline and with subsequent saliva samples, 87 (25%) acquired new infections over the 24 months. Sixty-eight of 87 people included in the clearance analysis (78%) cleared their oral HPV infections. Clearance was associated with being a nonsmoker (OR 12.7, 95% CI 1.3-122.8), and no previous diagnosis of a sexually transmitted infection (OR 6.2, 95% CI 2.0-19.9). New oral infections with HPV in this sample were not rare. Although most infections were cleared, clearance was not universal suggesting a reservoir of infection exists that might predispose to oropharyngeal carcinogenesis.This paper assesses the research literature on OFC in LMIC over the last decade across various geographical settings and project focus of the indexed literature. A scoping review of the indexed literature was performed using a set of predefined keywords. The articles were filtered by a ten-year time frame (2010-2019) and a strict inclusive-exclusive criterion. Two authors screened the titles/abstracts/full text of the final included papers and input the desired data (year of publication, type of publication, geographical country/region and project focus to a coded spreadsheet). Six hundred and twenty publications were inventoried from the indexed literature on OFC in LMIC settings over the 10-year period. Five hundred and eighty-three derived from single LMIC countries and 37 from multi-settings. More than half of the articles were reported from Asia (57%), then from Americas (22.8%), Africa (15.4%) and the rest from cross-regional, Europe and Oceania (4.9%). The top 3 LMIC contributors towards OFC publications were China (21.5%), Brazil (13.1%) and India (11.6%). The most discussed OFC project themes were prevalence, surgical repair, aetiology and genetics. This study helps OFC researchers, humanitarian missions and research grant funders to identify gaps in the literature on issues impacting on children and adults born with OFC, in which issues were subjected to research and which were less explored in which LMIC regions. In addition, this study offers recommendations for established OFC researchers and international research bodies to identify areas of deficiency in the literature and what information is required to support LMIC governments achieve SDGs by 2030.Platinum-based chemotherapy has been the cornerstone treatment for small cell lung cancer (SCLC) for decades, but no major progress has been made in the past 20 years with regard to overcoming chemoresistance. As the cell cycle checkpoint kinase 1 (Chk1) plays a key role in DNA damage response to chemotherapeutic drugs, we explored the mechanisms of acquired drug resistance to the Chk1 inhibitor prexasertib in SCLC. We established prexasertib resistance in two SCLC cell lines and found that DNA copy number, messengerRNA (mRNA) and protein levels of the cell cycle regulator Wee1 significantly correlate with the level of acquired resistance. Wee1 small interfering RNA (siRNA) or Wee1 inhibitor reversed prexasertib resistance, whereas Wee1 transfection induced prexasertib resistance in parental cells. Reverse phase protein microarray identified up-regulated proteins in the resistant cell lines that are involved in apoptosis, cell proliferation and cell cycle. Down-regulation of CDK1 and CDC25C kinases promoted acquired resistance in parental cells, whereas down-regulation of p38MAPK reversed the resistance. High Wee1 expression was significantly correlated with better prognosis of resected SCLC patients. Our results indicate that Wee1 overexpression plays an important role in acquired resistance to Chk1 inhibition. We also show that bypass activation of the p38MAPK signaling pathway may contribute to acquired resistance to Chk1 inhibition. The combination of Chk1 and Wee1 inhibitors may provide a new therapeutic strategy for the treatment of SCLC.