Factors associated with nosocomial SARS-CoV transmission among healthcare workers in Hanoi, Vietnam, 2003

BACKGROUND: In March of 2003, an outbreak of Severe Acute Respiratory Syndrome (SARS) occurred in Northern Vietnam. This outbreak began when a traveler arriving from Hong Kong sought medical care at a small hospital (Hospital A) in Hanoi, initiating a serious and substantial transmission event within the hospital, and subsequent limited spread within the community. METHODS: We surveyed Hospital A personnel for exposure to the index patient and for symptoms of disease during the outbreak. Additionally, serum specimens were collected and assayed for antibody to SARS-associated coronavirus (SARS-CoV) antibody and job-specific attack rates were calculated. A nested case-control analysis was performed to assess risk factors for acquiring SARS-CoV infection. RESULTS: One hundred and fifty-three of 193 (79.3%) clinical and non-clinical staff consented to participate. Excluding job categories with <3 workers, the highest SARS attack rates occurred among nurses who worked in the outpatient and inpatient general wards (57.1, 47.4%, respectively). Nurses assigned to the operating room/intensive care unit, experienced the lowest attack rates (7.1%) among all clinical staff. Serologic evidence of SARS-CoV infection was detected in 4 individuals, including 2 non-clinical workers, who had not previously been identified as SARS cases; none reported having had fever or cough. Entering the index patient's room and having seen (viewed) the patient were the behaviors associated with highest risk for infection by univariate analysis (odds ratios 20.0, 14.0; 95% confidence intervals 4.1–97.1, 3.6–55.3, respectively). CONCLUSION: This study highlights job categories and activities associated with increased risk for SARS-CoV infection and demonstrates that a broad diversity of hospital workers may be vulnerable during an outbreak. These findings may help guide recommendations for the protection of vulnerable occupational groups and may have implications for other respiratory infections such as influenza

Risk Factors for SARS Transmission from Patients Requiring Intubation: A Multicentre Investigation in Toronto, Canada

In the 2003 Toronto SARS outbreak, SARS-CoV was transmitted in hospitals despite adherence to infection control procedures. Considerable controversy resulted regarding which procedures and behaviours were associated with the greatest risk of SARS-CoV transmission.A retrospective cohort study was conducted to identify risk factors for transmission of SARS-CoV during intubation from laboratory confirmed SARS patients to HCWs involved in their care. All SARS patients requiring intubation during the Toronto outbreak were identified. All HCWs who provided care to intubated SARS patients during treatment or transportation and who entered a patient room or had direct patient contact from 24 hours before to 4 hours after intubation were eligible for this study. Data was collected on patients by chart review and on HCWs by interviewer-administered questionnaire. Generalized estimating equation (GEE) logistic regression models and classification and regression trees (CART) were used to identify risk factors for SARS transmission. ratio ≤59 (OR = 8.65, p = .001) were associated with increased risk of transmission of SARS-CoV. In CART analyses, the four covariates which explained the greatest amount of variation in SARS-CoV transmission were covariates representing individual patients.Close contact with the airway of severely ill patients and failure of infection control practices to prevent exposure to respiratory secretions were associated with transmission of SARS-CoV. Rates of transmission of SARS-CoV varied widely among patients

Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal.

The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors characterized by early fixation of multiple mutational and copy number drivers and rapid metastases to highly branched tumors with >10 subclonal drivers and extensive parallel evolution associated with attenuated progression. We identify genetic diversity and chromosomal complexity as determinants of patient outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance

Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies.

With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion in vivo, increasing the CD8+ to Treg cell ratio and promoting tumor rejection. Antibodies with improved FcγR binding profiles drove superior anti-tumor responses and survival. In patients with advanced melanoma, response to ipilimumab was associated with the CD16a-V158F high affinity polymorphism. Such activity only appeared relevant in the context of inflamed tumors, explaining the modest response rates observed in the clinical setting. Our data suggest that the activity of anti-CTLA-4 in inflamed tumors may be improved through enhancement of FcγR binding, whereas poorly infiltrated tumors will likely require combination approaches