Necrotizing soft tissue infections - a multicentre, prospective observational study (INFECT): protocol and statistical analysis plan.

BACKGROUND: The INFECT project aims to advance our understanding of the pathophysiological mechanisms in necrotizing soft tissue infections (NSTIs). The INFECT observational study is part of the INFECT project with the aim of studying the clinical profile of patients with NSTIs and correlating these to patient-important outcomes. With this protocol and statistical analysis plan we describe the methods used to obtain data and the details of the planned analyses. METHODS: The INFECT study is a multicentre, prospective observational cohort study. Patients with NSTIs are enrolled in five Scandinavian hospitals, which are all referral centres for NSTIs. The primary outcomes are the descriptive variables of the patients. Secondary outcomes include identification of factors associated with 90-day mortality and amputation; associations between affected body part, maximum skin defect and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score and 90-day mortality; 90-day mortality in patients with and without acute kidney injury (AKI) and LRINEC score of six and above or below six; and association between affected body part at arrival and microbiological findings. Exploratory outcomes include univariate analyses of baseline characteristics associations with 90-day mortality. The statistical analyses will be conducted in accordance with the predefined statistical analysis plan. CONCLUSION: Necrotizing soft tissue infections result in severe morbidity and mortality. The INFECT study will be the largest prospective study in patients with NSTIs to date and will provide important data for clinicians, researchers and policy makers on the characteristics and outcomes of these patients.

Biological activity and safety of adenoviral vector-expressed wild-type p53 after intratumoral injection in melanoma and breast cancer patients with p53-overexpressing tumors.

p53 mutations are common genetic alterations in human cancer. Gene transfer of a wild-type (wt) p53 gene reverses the loss of normal p53 function in vitro and in vivo. A phase I dose escalation study of single intratumoral (i.t.) injection of a replication-defective adenoviral expression vector containing wt p53 was carried out in patients with metastatic melanoma or breast cancer with increased p53 protein immunoreactivity in pretreatment tumor biopsies. The biological activity of the injected wt p53 was assayed by reverse transcriptase-polymerase chain reaction in tumor tissue. A total of six (five melanoma and one breast adenocarcinoma) patients were treated at dose levels dependent upon tumor size/dose escalation sequence. Five of six patients became positive for the transfer of wt p53 into tumor tissue 2 days after injection of the vector. Of the four patients assayed, all developed anti-adenoviral antibodies. Adverse reactions associated with i.t. injection were mild, with no obvious correlation between the incidence, severity, or relationship of the events and drug dose. p53 gene therapy by i.t. injection of a replication-defective adenoviral expression vector is safe, feasible, and biologically effective (with respect to transduction frequency) in patients with either metastatic melanoma or breast cancer.