Salmonella enterica Serovar Enteritidis,England and Wales, 1945–2011

In England and Wales, the emergence of Salmonella enterica serovar Enteritidis resulted in the largest and most persistent epidemic of foodborne infection attributable to a single subtype of any pathogen since systematic national microbiological surveillance was established. We reviewed 67 years of surveillance data to examine the features, underlying causes, and overall effects of S. enterica ser. Enteritidis. The epidemic was associated with the consumption of contaminated chicken meat and eggs, and a decline in the number of infections began after the adoption of vaccination and other measures in production and distribution of chicken meat and eggs. We estimate that >525,000 persons became ill during the course of the epidemic, which caused a total of 6,750,000 days of illness, 27,000 hospitalizations, and 2,000 deaths. Measures undertaken to control the epidemic have resulted in a major reduction in foodborne disease in England and Wales.     

Elevated tricuspid regurgitant jet velocity in subgroups of thalassemia patients: insight into pathophysiology and the effect of splenectomy

A high tricuspid regurgitant jet velocity (TRV) signifies a risk for or established pulmonary hypertension (PH), which is a serious complication in thalassemia patients. The underlying pathophysiology in thalassemia subgroups and potential biomarkers for early detection and monitoring are not well defined, in particular as they relate to spleen removal. To better understand some of these unresolved aspects, we examined 76 thalassemia patients (35 non-transfused), 25 splenectomized non-thalassemia patients (15 with hereditary spherocytosis), and 12 healthy controls. An elevated TRV (>2.5 m/s) was found in 25/76 (33 %) of the patients, confined to non-transfused or those with a late start of transfusions, including patients with hemoglobin H-constant spring, a finding not previously described. These non or late-transfused patients (76 % splenectomized) had significantly increased platelet activation (sCD40L), high platelet count, endothelial activation (endothelin-1), and hemolysis (LDH, plasma-free Hb), while hypercoagulable and inflammatory markers were not significantly increased. The same markers were increased in the seven patients with confirmed PH on cardiac catheterization, suggesting their possible role for screening patients at risk for PH. A combination of hemolysis and absence of spleen is necessary for developing a high TRV, as neither chronic hemolysis in the non-splenectomized thalassemia patients nor splenectomy without hemolysis, in the non-thalassemia patients, resulted in an increase in TRV.     

Density and Proximity of Fast Food Restaurants and Body Mass Index Among African Americans

Objectives. The purpose of this study was to address current gaps in the literature by examining the associations of fast food restaurant (FFR) density around the home and FFR proximity to the home, respectively, with body mass index (BMI) among a large sample of African American adults from Houston, Texas.Methods. We used generalized linear models with generalized estimating equations to examine associations of FFR density at 0.5-, 1-, 2-, and 5-mile road network buffers around the home with BMI and associations of the closest FFR to the home with BMI. All models were adjusted for a range of individual-level covariates and neighborhood socioeconomic status. We additionally investigated the moderating effects of household income on these relations. Data were collected from December 2008 to July 2009.Results. FFR density was not associated with BMI in the main analyses. However, FFR density at 0.5, 1, and 2 miles was positively associated with BMI among participants with lower incomes (P ≤ .025). Closer FFR proximity was associated with higher BMI among all participants (P < .001), with stronger associations emerging among those of lower income (P < .013) relative to higher income (P < .014).Conclusions. Additional research with more diverse African American samples is needed, but results supported the potential for the fast food environment to affect BMI among African Americans, particularly among those of lower economic means.Obesity and its associated health conditions are a growing problem in the United States, with obesity prevalence having more than doubled since the 1960s.1 The health care cost of Americans’ growing waistlines is substantial and expected to top $860 billion by 2030.2 Racial/ethnic disparities in obesity are of particular concern for the nation’s health, with African Americans experiencing the highest prevalence of obesity relative to other racial/ethnic groups.1 The National Health and Nutrition Examination Survey from 2009 to 2010 indicated that 38.8% of African American men and 58.5% of African American women were obese compared with 36.2% of non-Hispanic White men and 32.2% of non-Hispanic White women.3 Racial/ethnic disparities have also been cited for body mass index (BMI), with the gap in BMI growth widening between African Americans and Whites in recent decades.4To better understand the factors associated with these trends, researchers and policymakers are paying increased attention to the retail food environment. The growing availability of low-cost, calorie-dense consumables from fast food restaurants (FFRs) is one of the factors implicated in the nation’s rising BMI.5–7 The availability of FFRs may be particularly relevant to the growing racial/ethnic disparities in BMI because several studies support a higher density of FFRs among predominately African American neighborhoods relative to predominately White neighborhoods.8–11 Moreover, at least 1 study reports stronger relations between fast food availability and fast food consumption among non-White versus White populations.12 Thus, African Americans may be more likely to consume fast food if it is available, and it may be more available to them because FFRs tend to be clustered in African American neighborhoods. Not surprisingly, greater fast food consumption is associated with higher BMI.13–15Several studies examined associations between the availability of fast food and BMI. Fast food availability was most commonly conceptualized as the density of FFRs near a person’s home, work, or school environment. Findings about the associations of FFR density with BMI and overweight or obesity status, however, were mixed,5,11 with some studies supporting positive associations,16–19 and others citing null results.14,20 Less commonly, studies conceptualized fast food availability as the proximity of the closest FFR to a person’s home. Studies taking this approach yielded mixed results regarding relations between FFR proximity and fast food consumption,21,22 as well as between FFR proximity and BMI or obesity status.11,23 Unfortunately, most of these studies focused predominately on White populations, and many had methodological limitations (e.g., self-reported BMI) that could have contributed to mixed results.5,11 We found only a single study that focused on an all-African American sample, which yielded null results regarding associations between FFR density and BMI.24 Although this study had several strengths, including a sample of more than 4500 African Americans and investigator-measured BMI, limitations included only 1 conceptualization of FFR availability (FFR density), and the use of Euclidean distances (“as the crow flies”) in density buffer calculation, which may be less realistic than buffers based on road networks (i.e., the only places along which FFRs can be found).5 In addition, we found no previous studies that examined whether associations between FFR availability and BMI were moderated by household income. Because reasons cited for frequent fast food consumption include both accessibility and affordability,6 it might be that relations of FFRs and BMI are stronger among those of lower economic means for whom fast food might be more affordable than other dining options. Therefore, additional research is needed to better understand the relations of fast food availability and BMI among African Americans.The purpose of this study was to address current gaps in the literature by examining the associations of FFR density around the home and FFR proximity to the home, respectively, with BMI among a large sample of African American adults from Houston, Texas. We additionally investigated the moderating effects of household income on these relations.     

Vessel co‐option is common in human lung metastases and mediates resistance to anti‐angiogenic therapy in preclinical lung metastasis models

Anti‐angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti‐angiogenic therapies are poorly understood. Importantly, rather than utilizing angiogenesis, some metastases may instead incorporate pre‐existing vessels from surrounding tissue (vessel co‐option). As anti‐angiogenic therapies were designed to target only new blood vessel growth, vessel co‐option has been proposed as a mechanism that could drive resistance to anti‐angiogenic therapy. However, vessel co‐option has not been extensively studied in lung metastases, and its potential to mediate resistance to anti‐angiogenic therapy in lung metastases is not established. Here, we examined the mechanism of tumour vascularization in 164 human lung metastasis specimens (composed of breast, colorectal and renal cancer lung metastasis cases). We identified four distinct histopathological growth patterns (HGPs) of lung metastasis (alveolar, interstitial, perivascular cuffing, and pushing), each of which vascularized via a different mechanism. In the alveolar HGP, cancer cells invaded the alveolar air spaces, facilitating the co‐option of alveolar capillaries. In the interstitial HGP, cancer cells invaded the alveolar walls to co‐opt alveolar capillaries. In the perivascular cuffing HGP, cancer cells grew by co‐opting larger vessels of the lung. Only in the pushing HGP did the tumours vascularize by angiogenesis. Importantly, vessel co‐option occurred with high frequency, being present in >80% of the cases examined. Moreover, we provide evidence that vessel co‐option mediates resistance to the anti‐angiogenic drug sunitinib in preclinical lung metastasis models. Assuming that our interpretation of the data is correct, we conclude that vessel co‐option in lung metastases occurs through at least three distinct mechanisms, that vessel co‐option occurs frequently in lung metastases, and that vessel co‐option could mediate resistance to anti‐angiogenic therapy in lung metastases. Novel therapies designed to target both angiogenesis and vessel co‐option are therefore warranted. © 2016 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Prolongation of xenograft survival after combination therapy with 15-deoxyspergualin and total-lymphoid irradiation in the hamster-to-rat cardiac xenograft model.

Adequate immunosuppression remains a major obstacle to successful xenotransplantation, with early xenograft rejection appearing to be mediated by humoral factors. Total-lymphoid irradiation (TLI) and 15-deoxyspergualin (DOSP) have been shown to be effective immunosuppressive agents in allografs. In this study, TLI alone and in combination with DOSP and cyclosporine were evaluated in the hamster-to-rat heterotopic cardiac xenograft model. The animals were divided into four groups: group 1--control (n = 9); group 2--TLI alone, administered pretransplant at 125 cGy/day, four days per week, for three weeks (n = 12); group 3--TLI plus CsA at 10 mg/kg/day (n = 17); and group 4--TLI plus DOSP at 2.5 mg/kg/day (n = 10). Tissue sections were taken from rejected xenografts in all treatment groups for histological examination. Complement-dependent cytotoxicity assays were performed on the control group and also the TLI-DOSP group. The control animals were found to have a mean graft survival of 3.2 +/- 0.4 days. TLI alone (5.8 +/- 0.7 days) did not significantly improve graft survival in comparison with the control group. Combination of TLI with DOSP (26.3 +/- 5.9 days) results in significantly improved survival (P less than 0.05) in comparison with the control, TLI alone, and combination of TLI and CsA (13.6 +/- 8.6 days). Complement-dependent cytotoxicity assays revealed that control groups have low rat antihamster lymphocytotoxic antibody titer (1/1-1/10) prior to xenografting, and that these antibody titers show a precipitous rise to a level of 1/640-1/1280 by day 3, the time at which rejection occurred. This correlates with the histological findings of the rejected hearts showing a severe humoral type of rejection and no evidence of cellular rejection. In contrast, animals in the TLI-DOSP group had markedly lowered rat antihamster lymphocytotoxic antibody titers (1/20-1/40) on day 3, and these titers only increased to 1/160 at time of rejection. This correlates with the histological findings of a lesser degree of humoral rejection in the TLI-DOSP group. Combination therapy with TLI and DOSP results in a marked increase of survival in xenografts in this model not seen with any other drug combination studied in over 500 xenografts in our laboratory. This study indicates that TLI combined with DOSP results in prolonged suppression of the antixenograft antibody response. This combination of agents appears to have the potential to prevent early xenograft rejection.     

Differential Pathologic Variables and Outcomes across the Spectrum of Adenocarcinoma of the Esophagogastric Junction

Background  

Adenocarcinoma of the esophagogastric junction (AEG) as described by Siewert et al. is classified as one entity in the latest (7th Edition) American Joint Cancer Committee/International Union Against Cancer (AJCC/UICC) manual, compared with the previous mix of esophageal and gastric staging systems. The origin of AEG tumors, esophageal or gastric, and their biology remain controversial, particularly for AEG type II (cardia) tumors.     

The “O” sign

Abdominal Radiology -     

A phase I trial of pemetrexed plus gemcitabine given biweekly with B-vitamin support in solid tumor malignancies or advanced epithelial ovarian cancer

PURPOSE: To determine the maximally tolerated dose (MTD) of biweekly pemetrexed with gemcitabine plus B(12) and folate supplementation in patients with advanced solid tumors and ovarian cancer. EXPERIMENTAL DESIGN: Patients with no prior pemetrexed or gemcitabine therapy enrolled in cohorts of three, expanding to six if dose-limiting toxicity (DLT) was observed. Pemetrexed, escalated from to 700 mg/m(2), was given before gemcitabine 1,500 mg/m(2) every 14 days. DLTs were grade 4 neutropenia lasting >7 days or febrile neutropenia, grade 4 or 3 thrombocytopenia (with bleeding), grade > or =3 nonhematologic toxicity, or treatment delay of > or =1 week due to unresolved toxicity. RESULTS: The ovarian cancer cohort enrolled 24 patients with unlimited prior cytotoxic chemotherapies. MTD was observed at pemetrexed 600 mg/m(2), with 2 of 9 patients experiencing DLT. Most common grade 3 to 4 toxicities per patient were neutropenia (83%), leukopenia (67%), lymphopenia (73%), and febrile neutropenia (12%). Median cycle per patient was 8 (range, 1-16). Six of 21 (28%) patients had confirmed partial responses. Study protocol was modified for the solid tumor cohort (n = 30) to enroll patients with two or more prior cytotoxic regimens. MTD was observed at pemetrexed 500 mg/m(2), with 1 of 9 patients experiencing DLT. Most common grade 3 to 4 toxicities per patient were neutropenia (63%), lymphopenia (43%), leukopenia (70%) and febrile neutropenia (6.6%). Median cycle per patient was 4 (range, 1-20). Three of 29 (10.3%) response-evaluable patients had confirmed partial responses: 2 squamous cell carcinomas of head and neck and 1 nasopharyngeal cancer. CONCLUSION: MTDs for the solid tumor and ovarian cancer cohorts were reached at pemetrexed 500 and 600 mg/m(2), respectively, given biweekly with gemcitabine 1,500 mg/m(2).     

Isolated congenital tuberculosis otitis in a preterm infant

We report an unusual case of localized congenital tuberculosis otitis in a preterm infant. Unlike disseminated congenital cases, the manifestations of localized otitis are associated with a triad of signs: (i) regional lymphadenopathy in the absence of typical systemic features of tuberculosis; (ii) delayed onset of presentation; and (iii) refractory otitis unresponsive to conventional antimicrobial agents. The need for greater diligence in looking for neonatal tuberculosis is emphasized, especially in an ethnic or socioeconomic environment where the disease is prevalent. Congenital tuberculosis, otitis, preterm
PC Ng, Department of Paediatrics, Level 6, Clinical Sciences Building, Prince of Wales Hospital, Shatin, NT, Hong Kong