Peri-operative SARS-CoV-2 infection increases postoperative mortality. The aim of this study was to determine the optimal duration of planned delay before surgery in patients who have had SARS-CoV-2 infection. This international, multicentre, prospective cohort study included patients undergoing elective or emergency surgery during October 2020. Surgical patients with pre-operative SARS-CoV-2 infection were compared with those without previous SARS-CoV-2 infection. The primary outcome measure was 30-day postoperative mortality. Logistic regression models were used to calculate adjusted 30-day mortality rates stratified by time from diagnosis of SARS-CoV-2 infection to surgery. Among 140,231 patients (116 countries), 3127 patients (2.2%) had a pre-operative SARS-CoV-2 diagnosis. Adjusted 30-day mortality in patients without SARS-CoV-2 infection was 1.5% (95%CI 1.4-1.5). In patients with a pre-operative SARS-CoV-2 diagnosis, mortality was increased in patients having surgery within 0-2 weeks, 3-4 weeks and 5-6 weeks of the diagnosis (odds ratio (95%CI) 4.1 (3.3-4.8), 3.9 (2.6-5.1) and 3.6 (2.0-5.2), respectively). Surgery performed ≥ 7 weeks after SARS-CoV-2 diagnosis was associated with a similar mortality risk to baseline (odds ratio (95%CI) 1.5 (0.9-2.1)). After a ≥ 7 week delay in undertaking surgery following SARS-CoV-2 infection, patients with ongoing symptoms had a higher mortality than patients whose symptoms had resolved or who had been asymptomatic (6.0% (95%CI 3.2-8.7) vs. 2.4% (95%CI 1.4-3.4) vs. 1.3% (95%CI 0.6-2.0), respectively). Where possible, surgery should be delayed for at least 7 weeks following SARS-CoV-2 infection. Patients with ongoing symptoms ≥ 7 weeks from diagnosis may benefit from further delay.
Background Robust age-specific estimates of anal human papillomavirus (HPV) and high-grade squamous intraepithelial lesions (HSIL) in men can inform anal cancer prevention efforts. We aimed to evaluate the age-specific prevalence of anal HPV, HSIL, and their combination, in men, stratified by HIV status and sexuality.
MethodsWe did a systematic review for studies on anal HPV infection in men and a pooled analysis of individuallevel data from eligible studies across four groups: HIV-positive men who have sex with men (MSM), HIV-negative MSM, HIV-positive men who have sex with women (MSW), and HIV-negative MSW. Studies were required to inform on type-specific HPV infection (at least HPV16), detected by use of a PCR-based test from anal swabs, HIV status, sexuality (MSM, including those who have sex with men only or also with women, or MSW), and age. Authors of eligible studies with a sample size of 200 participants or more were invited to share deidentified individual-level data on the above four variables. Authors of studies including 40 or more HIV-positive MSW or 40 or more men from Africa (irrespective of HIV status and sexuality) were also invited to share these data. Pooled estimates of anal high-risk HPV (HR-HPV, including HPV16,
The E7 tumor antigen of human papillomavirus type 16 (HPV16) is a validated target for immunodiagnosis and immunotherapy of HPV-associated cervical cancer. Anti-HPV16 E7 antibodies in scFv format were isolated from a human antibody phage display library and characterized. With the aim of interfering with the oncogenic activity of E7 protein, the most reactive of the selected antibody fragments was expressed by eukaryotic vectors in different compartments of the HPV16-positive cervical carcinoma SiHa cell line. The intracellular antibodies (intrabodies) were tested for their ability of inhibiting cell proliferation. A significant inhibition was obtained targeting the intrabodies to the nuclear and secretory compartments whereas no significant effect was observed in case of cytoplasmic localization. Inhibition was highly specific as no antiproliferative effect was obtained either with the E7-specific intrabodies in HPV-negative cells nor with irrelevant intrabodies in SiHa cells. ' 2005 Wiley-Liss, Inc.Key words: human papillomavirus; E7 protein; intrabodies; singlechain variable fragment; antiproliferative effect; cervical cancer The HPV16 is involved in the aetiology of cervical cancer, the second main cause of cancer mortality in women worldwide.1,2 A real need exists to counter HPV infections either by prevention or by therapy. Many prophylactic and therapeutic vaccine strategies are currently under development or in clinical trial.
3,4The HPV16 oncoproteins E6 and E7, expressed in cervical carcinoma, are crucial for the development and the maintenance of the malignant phenotype.1 These antigens are valuable targets for immunotherapy of tumors because they are able to elicit CTLmediated tumor rejection.5 The HPV16 E7 has been shown recently to elicit antitumoral immunity in mice even when expressed in Nicotiana benthamiana plants. 6 This protein binds several tumour suppressors and promotes keratinocyte transformation by favoring DNA synthesis or inhibiting cellular differentiation.7-9 Several approaches have been explored to interfere with the HPV-induced abnormal proliferation by blocking the E7 activity at either gene or protein level, e.g., by phosphorothioate oligonucleotides, 10 short interfering RNA 11 and aptamers. 12 Intracellular immunization has provided new chances for interfering with the function of predetermined intracellular targets by directing antibodies in scFv format to specific compartments of mammalian cells. 13 The intracellular antibodies (intrabodies) can specifically recognize the target antigen in the intracellular environment and counteract its function with a not yet clarified mechanism of action, spanning from forming antigen-antibody complexes to diverting the target-antigen to unusual compartments.14 This approach has been employed already to achieve antineoplastic effects using intrabodies targeting oncogenic proteins.15 Evidence of antineoplastic effects was obtained in HPV16-positive human carcinoma cell lines by a hybridoma-derived recombinant scFv specific for the HPV16 E7...
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