No abstract

We investigated a multistate outbreak of Escherichia coli O157:H7 infections. Isolates from 13 case patients from California, Nevada, and Arizona were matched by pulsed-field gel electrophoresis subtyping. Five case patients (38%) were hospitalized, and 3 (23%) developed hemolytic uremic syndrome; none died. The median age was 12 years (range, 2-75 years), and 10 (77%) were female. Case-control studies found an association between illness and eating beef tacos at a national Mexican-style fast-food restaurant chain (88% of cases versus 38% of controls; matched OR, undefined; 95% confidence interval, 1.49 to infinity; P=.009). A trace-back investigation implicated an upstream supplier of beef, but a farm investigation was not possible. This outbreak illustrates the value of employing hospital laboratory-based surveillance to detect local clusters of infections and the effectiveness of using molecular subtyping to identify geographically dispersed outbreaks. The outbreak investigation also highlights the need for a more efficient tracking system for food products.

Background: ENKTL account for more than 20% of the peripheral T-cell lymphoma in Asia. Patients with r/r ENKTL have a poor prognosis after failing an L-asparaginase based regimen, and the median overall survival is less than 6 months. The overexpression of PD-L1 induced by EBV infection is a potential mechanism for ENKTL to avert immune surveillance, and recent studies of PD-1 antibodies in pts with r/r ENKTL have demonstrated potential efficacy. Sintilimab, a fully human anti-PD-1 monoclonal antibody, has a safety profile consistent with other approved PD-1 antibodies and was approved for r/r classical Hodgkin lymphoma in China in 2018. Aims: This multicenter, single-arm, phase 2 study aims to validate the efficacy and safety of sintilimab monotherapy in patients with r/r EN-KTL in China. Methods: Patients with pathologically confirmed r/r ENKTL were enrolled. Sintilimab was given 200 mg IV Q3W, until PD, death, unacceptable toxicity, or withdrawal from the study. Treatment beyond PD is allowed. Tumor response evaluation was performed by both PET-CT and CT/MRI with contrast. The primary endpoint was objective response rate based on LUGANO 2014 criteria. Data cut-off date for this analysis was Feb 2, 2019. Results: From Aug 31, 2017 to Feb 7, 2018, a total of 28 patients were enrolled: 60.7% male and the median age was 37 (range: 19~65) yr. Sixty-eight percent of patients were stage IV and 89.3% were ECOG PS  1. All patients had failed an L-asparaginase based regimen, the median lines of previous therapy were 3 (range: 1~13), 78.6% patients received prior radiotherapy and 7.1% had failed HSCT. Median duration of therapy was 14.04 (range: 1.4~17.3) months and 19 patients are still receiving sintilimab. Sixty-eight percent (19/28, 95%CI: 47.6%~84.1%) of patients achieved response (CR+PR), including 4 pts who experienced PD prior to having a response. DCR was 85.7%, including 5 pts who experienced PD before SD or response. The 1-year OS rate was 82.1% and the median OS has not been reached. Most TRAEs were G1~2 (67.9%) and no patients discontinued treatment due to AEs. The most common TRAE was decreased lymphocyte count (46.4%) and 84.6% were grade 1~2. SAEs occurred in 21.4% of patients and none were related to sintilimab. No patients died from AEs. Summary/Conclusion: Sintilimab is effective and well tolerated in r/r ENKTL and could be a promising treatment option for these patients. Early disease progression observed by PET scan in this study could be pseudo-progression as it did not correlate with poor outcome, which warrants further investigation. NCT03228836

Susceptibility to environmental pollutants involves both biological and nonbiobgical factors. Individuals belonging to minority groups are much more likely to be subject to a number of these factors. This paper examines biological susceptibility of minorities to environmental pollutants and provides specific examples of susceptibility resulting from: genetic makeup; occupation; other factors such as compromised health status, exposure to mixtures of pollutants, substance abuse, and unemployment; and social inequality of access to health care, education, and communication skills. Recommendations are made for specific actions and for additional studies.

In radiotherapy for prostate cancer irradiation of neighboring organs at risk may lead to undesirable side-effects. Given this setting, the bladder presents the largest inter-fraction shape variations hampering the computation of the actual delivered dose vs. planned dose. This paper proposes a population model, based on longitudinal data, able to estimate the probability of bladder presence during treatment, using only the planning computed tomography (CT) scan as input information. As in previously-proposed principal component analysis (PCA) population-based models, we have used the data to obtain the dominant eigenmodes that describe bladder geometric variations between fractions. However, we have used a longitudinal analysis along each mode in order to properly characterize patient's variance from the total population variance. We have proposed is a mixed-effects (ME) model in order to separate intra- and inter-patient variability, in an effort to control confounding cohort effects. Other than using PCA, bladder shapes are represented by using spherical harmonics (SPHARM) that additionally enables data compression without information lost. Based on training data from repeated CT scans, the ME model was thus implemented following dimensionality reduction by means of SPHARM and PCA. We have evaluated the model in a leave-one-out cross validation framework on the training data but also using independent data. Probability maps (PMs) were thus generated with several draws from the learnt model as predicted regions where the bladder will likely move and deform. These PMs were compared with the actual regions using metrics based on mutual information distance and misestimated voxels. The prediction was also compared with two previous population PCA-based models. The proposed model was able to reduce the uncertainties in the estimation of the probable region of bladder motion and deformation. This model can thus be used for tailoring radiotherapy treatments.