A retrospective study of R-DHAP/Ox for early progressing follicular lymphoma

R-DHAP/Ox; autologous transplantation; early disease progression; follicular lymphom

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease

Modifiable and non-modifiable factors related to HPV infection and cervical abnormalities in women at high risk: a cross-sectional analysis from the Valhidate Study

Abstract: Migrant women, and women infected with HIV, are at enhanced risk of cervical HPV infection and HPV-related cancers. We investigated factors that can reduce these risks through public health preventive and screening interventions. We compared prevalence and risk factors for cervical HPV infection/lesions in women with HIV-infection (HIW) and migrant women (RMW) with a control group of resident women (SPW) who were enrolled in the study for the eVALuation and monitoring of HPV Infections and relATEd cervical diseases in high-risk women (VALHIDATE). Among 3093 evaluable women, age-standardized HPV prevalence was 36.3% (95%CI: 28.1–44.4) in HIW, 21.6% (95%CI: 15.7–27.5) in RMW, and 14.3% (95%CI: 12.5–16.1) in SPW. Adjusted prevalence of HPV infection was 2.07 times higher among HIW (95%CI: 1.75–2.45), and 1.45 times higher among RMW (95%CI: 1.17–1.80) than in SPW. Prevalence-ratios of SIL and HG-SIL were 2.67 (95%CI: 2.06–3.45) and 2.82 (95%CI: 1.28–6.20), respectively, in HIW compared to controls. A multivariate log-binomial regression model showed modifiable risk factors associated with HPV infection/lesion to have different patterns among groups. Specific public-health intervention, including health and sexual-health education, safe-sex procedures, and improvements to screening programmes, could favorably affect these highly vulnerable women

Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity

Here, we describe the identification of a clinical candidate via structure-based optimization of a ligand efficient pyrazole-benzimidazole fragment. Aurora kinases play a key role in the regulation of mitosis and in recent years have become attractive targets for the treatment of cancer. X-ray crystallographic structures were generated using a novel soakable form of Aurora A and were used to drive the optimization toward potent (IC50 ≈ 3 nM) dual Aurora A/Aurora B inhibitors. These compounds inhibited growth and survival of HCT116 cells and produced the polyploid cellular phenotype typically associated with Aurora B kinase inhibition. Optimization of cellular activity and physicochemical properties ultimately led to the identification of compound 16 (AT9283). In addition to Aurora A and Aurora B, compound 16 was also found to inhibit a number of other kinases including JAK2 and Abl (T315I). This compound demonstrated in vivo efficacy in mouse xenograft models and is currently under evaluation in phase I clinical trials

Impact of severe acute respiratory syndrome coronavirus-2 infection on the outcome of primary central nervous system lymphoma treatment: A study of the International PCNSL Collaborative Group

To optimise management of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection identifying high-risk patients and maintaining treatment dose intensity is an important issue in patients with aggressive lymphomas. In the present study, we report on the presentation, management, and outcome of an international series of 91 patients with primary central nervous system lymphoma and SARS-CoV-2 infection. SARS-CoV-2 was diagnosed before/during first-line treatment in 64 patients, during follow-up in 21, and during salvage therapy in six. Among the 64 patients infected before/during first-line chemotherapy, 38 (59%) developed pneumonia and 26 (41%) did not clear the virus. Prolonged exposure to steroids before viral infection and/or treatment with high-dose cytarabine favoured pneumonia development and virus persistence and were associated with poorer survival; 81% of patients who did not clear virus died early from coronavirus disease 2019 (COVID-19). Vaccination was associated with lower pneumonia incidence and in-hospital mortality. Chemotherapy was initiated/resumed in 43 (67%) patients, more commonly among patients who did not develop pneumonia, cleared the virus, or did not receive steroids during infection. Chemotherapy resumption in patients with viral persistence should be indicated cautiously as it was associated with a poorer survival (6-month, 70% and 87%, p = 0.07). None of the 21 patients infected during follow-up died from COVID-19, requiring similar measures as infected subjects in the general population

Hepatitis C virus positive diffuse large B-cell lymphomas have distinct molecular features and lack BCL2 translocations

The clinical presentation of patients with hepatitis C virus (HCV)-positive diffuse large B-cell lymphoma (DLBCL) is different from their HCV-negative counterparts, but the underlying molecular and pathological characteristics are largely under investigated. The virus has a role in lymphomagenesis, as witnessed by the curative potential of antiviral therapy in HCV-related low-grade B-cell lymphomas