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The efficacy of the Enteric Pathogen Screen (EPS) card as a rapid method for identification of Salmonella spp. isolated in stool cultures was studied. Of the 120 lactose-negative, sucrose-negative, HS-producing colonies tested, 74 were identified as Salmonella enteritidis by conventional methods. The reading of the EPS card after 2 h of incubation yielded a sensitivity of 47.2% and a specificity and positive predictive value of 100%, with a negative predictive value of 54.1%. In the final reading of 4 h, a sensitivity of 97.2% and a specificity of 86.9% were obtained, with a positive predictive value of 92.3% and a negative predictive value of 95.2%. [ABSTRACT FROM AUTHOR]

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and three additional alcohol-related signatures indicating synergism between the two exposures. Tobacco smoking was associated with differences in the mutational spectra and repertoire of driver mutations in cancer genes, and in patterns of copy number change. Together, the results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.

Management of hepatoblastoma (HB), the most frequent pediatric liver cancer, is based on surgical resection and perioperative chemotherapy regimens. In this study, we aimed to identify actionable targets in HB and assess the efficacy of molecular therapies in preclinical models of HB. Paired tumor and adjacent tissues from 31 HBs and a validation set of 50 HBs were analyzed using RNA-seq, SNP, and methylation arrays. IGF2 overexpression was identified as the top targetable HB driver, present in 71% of HBs (22/31). IGF2high tumors displayed progenitor cell features and shorter recurrence-free survival. IGF2 overexpression was associated in 91% of cases with fetal promoter hypomethylation, ICR1 deregulation, 11p15.5 loss of heterozygosity or miR483-5p overexpression. The antitumor effect of xentuzumab (a monoclonal antibody targeting IGF1/2) alone or in combination with the conventional therapeutic agent cisplatin was assessed in HB cell lines, in PDX-derived HB organoids and in a xenograft HB murine model. The combination of xentuzumab with cisplatin showed strong synergistic antitumor effects in organoids and in IGF2high cell lines. In mice (n = 55), the combination induced a significant decrease in tumor volume and improved survival compared with cisplatin alone. These results suggest that IGF2 is an HB actionable driver and that, in preclinical models of HB, the combination of IGF1/2 inhibition with cisplatin induces superior antitumor effects than cisplatin monotherapy. Overall, our study provides a rationale for testing IGF2 inhibitors in combination with cisplatin in HB patients with IGF2 overexpression., (©2023 American Association for Cancer Research.)

Objective: We previously reported a characterisation of the hepatocellular carcinoma (HCC) immune contexture and described an immune-specific class. We now aim to further delineate the immunogenomic classification of HCC to incorporate features that explain responses/resistance to immunotherapy., Design: We performed RNA and whole-exome sequencing, T-cell receptor (TCR)-sequencing, multiplex immunofluorescence and immunohistochemistry in a novel cohort of 240 HCC patients and validated our results in other cohorts comprising 660 patients., Results: Our integrative analysis led to define: (1) the inflamed class of HCC (37%), which includes the previously reported immune subclass (22%) and a new immune-like subclass (15%) with high interferon signalling, cytolytic activity, expression of immune-effector cytokines and a more diverse T-cell repertoire. A 20-gene signature was able to capture ~90% of these tumours and is associated with response to immunotherapy. Proteins identified in liquid biopsies recapitulated the inflamed class with an area under the ROC curve (AUC) of 0.91; (2) The intermediate class, enriched in TP53 mutations (49% vs 29%, p=0.035), and chromosomal losses involving immune-related genes and; (3) the excluded class, enriched in CTNNB1 mutations (93% vs 27%, p<0.001) and PTK2 overexpression due to gene amplification and promoter hypomethylation. CTNNB1 mutations outside the excluded class led to weak activation of the Wnt-βcatenin pathway or occurred in HCCs dominated by high interferon signalling and type I antigen presenting genes., Conclusion: We have characterised the immunogenomic contexture of HCC and defined inflamed and non-inflamed tumours. Two distinct CTNNB1 patterns associated with a differential role in immune evasion are described. These features may help predict immune response in HCC., Competing Interests: Competing interests: JA and JN are staff scientists from Bristol-Myers Squibb. JML is receiving research support from Bayer HealthCare Pharmaceuticals, Eisai Inc, Bristol-Myers Squibb, Boehringer-Ingelheim and Ipsen, and consulting fees from Eli Lilly, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Eisai Inc, Celsion Corporation, Exelixis, Merck, Ipsen, Genentech, Roche, Glycotest, Nucleix, Sirtex, Mina Alpha Ltd and AstraZeneca. The remaining coauthors have nothing to disclose related to this manuscript., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Mongolia has the world's highest incidence of hepatocellular carcinoma (HCC), with ∼100 cases/100,000 inhabitants, although the reasons for this have not been thoroughly delineated., Experimental Design: We performed a molecular characterization of Mongolian (n = 192) compared with Western (n = 187) HCCs by RNA sequencing and whole-exome sequencing to unveil distinct genomic and transcriptomic features associated with environmental factors in this population., Results: Mongolian patients were younger, with higher female prevalence, and with predominantly HBV-HDV coinfection etiology. Mongolian HCCs presented significantly higher rates of protein-coding mutations (121 vs. 70 mutations per tumor in Western), and in specific driver HCC genes (i.e., APOB and TSC2). Four mutational signatures characterized Mongolian samples, one of which was novel (SBS Mongolia) and present in 25% of Mongolian HCC cases. This signature showed a distinct substitution profile with a high proportion of T>G substitutions and was significantly associated with a signature of exposure to the environmental agent dimethyl sulfate (71%), a 2A carcinogenic associated with coal combustion. Transcriptomic-based analysis delineated three molecular clusters, two not present in Western HCC; one with a highly inflamed profile and the other significantly associated with younger female patients., Conclusions: Mongolian HCC has unique molecular traits with a high mutational burden and a novel mutational signature associated with genotoxic environmental factors present in this country., (©2022 American Association for Cancer Research.)

Purpose: Immune checkpoint inhibitors combined with antiangiogenic agents produce benefits in the treatment of advanced hepatocellular carcinoma (HCC). We investigated the efficacy and immunomodulatory activity of cabozantinib alone and combined with anti-PD1 in experimental models of HCC, and explored the potential target population that might benefit from this combination., Experimental Design: C57BL/6J mice bearing subcutaneous Hepa1-6 or Hep53.4 tumors received cabozantinib, anti-PD1, their combination, or placebo. Tumor and blood samples were analyzed by flow cytometry, IHC, transcriptome, and cytokine profiling. Cabozantinib-related effects were validated in a colorectal cancer patient-derived xenograft model. Transcriptomic data from three human HCC cohorts (cohort 1: n = 167, cohort 2: n = 57, The Cancer Genome Atlas: n = 319) were used to cluster patients according to neutrophil features, and assess their impact on survival., Results: The combination of cabozantinib and anti-PD1 showed increased antitumor efficacy compared with monotherapy and placebo (P < 0.05). Cabozantinib alone significantly increased neutrophil infiltration and reduced intratumor CD8+PD1+ T-cell proportions, while the combination with anti-PD1 further stimulated both effects and significantly decreased regulatory T cell (Treg) infiltration (all P < 0.05). In blood, cabozantinib and especially combination increased the proportions of overall T cells (P < 0.01) and memory/effector T cells (P < 0.05), while lowering the neutrophil-to-lymphocyte ratio (P < 0.001 for combination). Unsupervised clustering of human HCCs revealed that high tumor enrichment in neutrophil features observed with the treatment combination was linked to less aggressive tumors with more differentiated and less proliferative phenotypes., Conclusions: Cabozantinib in combination with anti-PD1 enhanced antitumor immunity by bringing together innate neutrophil-driven and adaptive immune responses, a mechanism of action which favors this approach for HCC treatment., (©2022 American Association for Cancer Research.)

Background and Aims: Lenvatinib is an effective drug in advanced HCC. Its combination with the anti-PD1 (programmed cell death protein 1) immune checkpoint inhibitor, pembrolizumab, has generated encouraging results in phase Ib and is currently being tested in phase III trials. Here, we aimed to explore the molecular and immunomodulatory effects of lenvatinib alone or in combination with anti-PD1., Approach and Results: We generated three syngeneic models of HCC in C57BL/6J mice (subcutaneous and orthotopic) and randomized animals to receive placebo, lenvatinib, anti-PD1, or combination treatment. Flow cytometry, transcriptomic, and immunohistochemistry analyses were performed in tumor and blood samples. A gene signature, capturing molecular features associated with the combination therapy, was used to identify a subset of candidates in a cohort of 228 HCC patients who might respond beyond what is expected for monotherapies. In mice, the combination treatment resulted in tumor regression and shorter time to response compared to monotherapies (P < 0.001). Single-agent anti-PD1 induced dendritic and T-cell infiltrates, and lenvatinib reduced the regulatory T cell (Treg) proportion. However, only the combination treatment significantly inhibited immune suppressive signaling, which was associated with the TGFß pathway and induced an immune-active microenvironment (P < 0.05 vs. other therapies). Based on immune-related genomic profiles in human HCC, 22% of patients were identified as potential responders beyond single-agent therapies, with tumors characterized by Treg cell infiltrates, low inflammatory signaling, and VEGFR pathway activation., Conclusions: Lenvatinib plus anti-PD1 exerted unique immunomodulatory effects through activation of immune pathways, reduction of Treg cell infiltrate, and inhibition of TGFß signaling. A gene signature enabled the identification of ~20% of human HCCs that, although nonresponding to single agents, could benefit from the proposed combination., (© 2021 by the American Association for the Study of Liver Diseases.)

Adeno-associated virus (AAV) integrates into host genomes at low frequency, but when integration occurs in oncogenic hotspots it can cause hepatocellular carcinoma (HCC). Given the possibility of recombinant AAV (rAAV) integration leading to HCC, common causes of liver inflammation like non-alcoholic fatty liver disease (NAFLD) may increase the risk of rAAV-induced HCC. A rAAV targeting the oncogenic mouse Rian locus was used, and as expected led to HCC in all mice infected as neonates, likely due to growth-related hepatocyte proliferation in young mice. Mice infected with rAAV as adults did not develop HCC unless they were fed a diet leading to NAFLD, with increased inflammation and hepatocyte proliferation. Female mice were less susceptible to rAAV-induced HCC, and male mice with NAFLD treated with estrogen exhibited less inflammation and immune exhaustion associated with oncogenesis compared to those without estrogen. Adult NAFLD mice infected with a non-targeted control rAAV also developed HCC, though only half as frequently as those exposed to the Rian targeted rAAV. This study shows that adult mice exposed to rAAV gene therapy in the context of chronic liver disease developed HCC at high frequency, and thus warrants further study in humans given the high prevalence of NAFLD in the population., (Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Purpose: Chromosomal instability is a hallmark of cancer that results in broad and focal copy-number alterations (CNAs), two events associated with distinct molecular, immunologic, and clinical features. In hepatocellular carcinoma (HCC), the role of CNAs has not been thoroughly assessed. Thus, we dissected the impact of CNA burdens on HCC molecular and immune features., Experimental Design: We analyzed SNP array data from 452 paired tumor/adjacent resected HCCs and 25 dysplastic nodules. For each sample, broad and focal CNA burdens were quantified using CNApp, and the resulting broad scores (BS) and focal scores (FS) were correlated with transcriptomic, mutational, and methylation profiles, tumor immune composition, and clinicopathologic data., Results: HCCs with low broad CNA burdens (defined as BS ≤ 4; 17%) presented high inflammation, active infiltrate signaling, high cytolytic activity, and enrichment of the "HCC immune class" and gene signatures related to antigen presentation. Conversely, tumors with chromosomal instability (high broad CNA loads, BS ≥ 11; 40%), displayed immune-excluded traits and were linked to proliferation, TP53 dysfunction, and DNA repair. Candidate determinants of the low cytotoxicity and immune exclusion features of high-BS tumors included alterations in antigen-presenting machinery (i.e., HLA), widespread hypomethylation, and decreased rates of observed/expected neoantigenic mutations. High FSs were independent of tumor immune features, but were related to proliferation, TP53 dysfunction, and progenitor cell traits., Conclusions: HCCs with high chromosomal instability exhibit features of immune exclusion, whereas tumors displaying low burdens of broad CNAs present an immune active profile. These CNA scores can be tested to predict response to immunotherapies., (©2020 American Association for Cancer Research.)

Background & Aims: Hepatoblastoma (HB) is a rare disease. Nevertheless, it is the predominant pediatric liver cancer, with limited therapeutic options for patients with aggressive tumors. Herein, we aimed to uncover the mechanisms of HB pathobiology and to identify new biomarkers and therapeutic targets in a move towards precision medicine for patients with advanced HB., Methods: We performed a comprehensive genomic, transcriptomic and epigenomic characterization of 159 clinically annotated samples from 113 patients with HB, using high-throughput technologies., Results: We discovered a widespread epigenetic footprint of HB that includes hyperediting of the tumor suppressor BLCAP concomitant with a genome-wide dysregulation of RNA editing and the overexpression of mainly non-coding genes of the oncogenic 14q32 DLK1-DIO3 locus. By unsupervised analysis, we identified 2 epigenomic clusters (Epi-CA, Epi-CB) with distinct degrees of DNA hypomethylation and CpG island hypermethylation that are associated with the C1/C2/C2B transcriptomic subtypes. Based on these findings, we defined the first molecular risk stratification of HB (MRS-HB), which encompasses 3 main prognostic categories and improves the current clinical risk stratification approach. The MRS-3 category (28%), defined by strong 14q32 locus expression and Epi-CB methylation features, was characterized by CTNNB1 and NFE2L2 mutations, a progenitor-like phenotype and clinical aggressiveness. Finally, we identified choline kinase alpha as a promising therapeutic target for intermediate and high-risk HBs, as its inhibition in HB cell lines and patient-derived xenografts strongly abrogated tumor growth., Conclusions: These findings provide a detailed insight into the molecular features of HB and could be used to improve current clinical stratification approaches and to develop treatments for patients with HB., Lay Summary: Hepatoblastoma is a rare childhood liver cancer that has been understudied. We have used cutting-edge technologies to expand our molecular knowledge of this cancer. Our biological findings can be used to improve clinical management and pave the way for the development of novel therapies for this cancer., Competing Interests: Conflict of interest Prof. Josep M. Llovet is receiving research support from Bayer HealthCare Pharmaceuticals, Eisai Inc, Bristol-Myers Squibb and Ipsen, and consulting fees from Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Eisai Inc, Celsion Corporation, Eli Lilly, Exelixis, Merck, Ipsen, Glycotest, Navigant, Leerink Swann LLC, Midatech Ltd, Fortress Biotech, Sprink Pharmaceuticals and Nucleix and CANFITE. CA has a research contract with CHIOME Biosciences Inc. The other authors report no conflicts of interest in this work. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objective: Central nervous system (CNS) features in children with permanent neonatal diabetes (PNDM) due to KCNJ11 mutations have a major impact on affected families. Sulfonylurea therapy achieves outstanding metabolic control but only partial improvement in CNS features. The effects of KCNJ11 mutations on the adult brain and their functional impact are not well understood. We aimed to characterize the CNS features in adults with KCNJ11 PNDM compared with adults with INS PNDM., Research Design and Methods: Adults with PNDM due to KCNJ11 mutations ( n = 8) or INS mutations ( n = 4) underwent a neurological examination and completed standardized neuropsychological tests/questionnaires about development/behavior. Four individuals in each group underwent a brain MRI scan. Test scores were converted to Z scores using normative data, and outcomes were compared between groups., Results: In individuals with KCNJ11 mutations, neurological examination was abnormal in seven of eight; predominant features were subtle deficits in coordination/motor sequencing. All had delayed developmental milestones and/or required learning support/special schooling. Half had features and/or a clinical diagnosis of autism spectrum disorder. KCNJ11 mutations were also associated with impaired attention, working memory, and perceptual reasoning and reduced intelligence quotient (IQ) (median IQ KCNJ11 vs. INS mutations 76 vs. 111, respectively; P = 0.02). However, no structural brain abnormalities were noted on MRI. The severity of these features was related to the specific mutation, and they were absent in individuals with INS mutations., Conclusions: KCNJ11 PNDM is associated with specific CNS features that are not due to long-standing diabetes, persist into adulthood despite sulfonylurea therapy, and represent the major burden from KCNJ11 mutations., (© 2018 by the American Diabetes Association.)

Background & Aims: Mixed hepatocellular cholangiocarcinoma (HCC-CCA) is a rare and poorly understood type of primary liver cancer. We aimed to perform a comprehensive molecular characterization of this malignancy., Methods: Gene expression profiling, DNA copy number detection, and exome sequencing using formalin-fixed samples from 18 patients with mixed HCC-CCA were performed, encompassing the whole histological spectrum of the disease. Comparative genomic analysis was carried out, using independent datasets of HCC (n=164) and intrahepatic cholangiocarcinoma (iCCA) (n=149)., Results: Integrative genomic analysis of HCC-CCAs revealed that cholangiolocellular carcinoma (CLC) represents a distinct biliary-derived entity compared with the stem-cell and classical types. CLC tumors were neural cell adhesion molecule (NCAM) positive (6/6 vs. 1/12, p<0.001), chromosomally stable (mean chromosomal aberrations 5.7 vs. 14.1, p=0.008), showed significant upregulation of transforming growth factor (TGF)-β signaling and enrichment of inflammation-related and immune response signatures (p<0.001). Stem-cell tumors were characterized by spalt-like transcription factor 4 (SALL4) positivity (6/8 vs. 0/10, p<0.001), enrichment of progenitor-like signatures, activation of specific oncogenic pathways (i.e., MYC and insulin-like growth factor [IGF]), and signatures related to poor clinical outcome. In the classical type, there was a significant correlation in the copy number variation of the iCCA and HCC components, suggesting a clonal origin. Exome sequencing revealed an average of 63 non-synonymous mutations per tumor (2 mean driver mutations per tumor). Among those, TP53 was the most frequently mutated gene (6/21, 29%) in HCC-CCAs., Conclusions: Mixed HCC-CCA represents a heterogeneous group of tumors, with the stem-cell type characterized by features of poor prognosis, and the classical type with common lineage for HCC and iCCA components. CLC stands alone as a distinct biliary-derived entity associated with chromosomal stability and active TGF-β signaling., Lay Summary: Molecular analysis of mixed hepatocellular cholangiocarcinoma (HCC-CCA) showed that cholangiolocellular carcinoma (CLC) is distinct and biliary in origin. It has none of the traits of hepatocellular carcinoma (HCC). However, within mixed HCC-CCA, stem-cell type tumors shared an aggressive nature and poor outcome, whereas the classic type showed a common cell lineage for both the HCC and the intrahepatic CCA component. The pathological classification of mixed HCC-CCA should be redefined because of the new molecular data provided., (Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The cerebellar cognitive affective syndrome (CCAS) was first described by Schmahmann and Sherman as a constellation of symptoms including dysexecutive syndrome, spatial cognitive deficit, linguistic deficits and behavioural abnormalities in patients with a lesion in the cerebellum with otherwise normal brain. Neurosurgical patients with cerebellar tumours constitute one of the cohorts in which the CCAS has been described. In this paper, we present a critical review of the literature of this syndrome in neurosurgical patients. Thereafter, we present a prospective clinical study of 10 patients who underwent posterior fossa tumour resection and had a detailed post-operative neuropsychological, neuropsychiatric and neuroradiological assessment. Because our findings revealed a large number of perioperative neuroradiological confounding variables, we reviewed the neuroimaging of a further 20 patients to determine their prevalence. Our literature review revealed that study design, methodological quality and sometimes both diagnostic criteria and findings were inconsistent. The neuroimaging study (pre-operative, n = 10; post-operative, n = 10) showed very frequent neuroradiological confounding complications (e.g. hydrocephalus; brainstem compression; supratentorial lesions and post-operative subdural hygroma); the impact of such features had largely been ignored in the literature. Findings from our clinical study showed various degree of deficits in neuropsychological testing (n = 1, memory; n = 3, verbal fluency; n = 3, attention; n = 2, spatial cognition deficits; and n = 1, behavioural changes), but no patient had full-blown features of CCAS. Our study, although limited, finds no robust evidence of the CCAS following surgery. This and our literature review highlight a need for guidelines regarding study design and methodology when attempting to evaluate neurosurgical cases with regard to the potential CCAS.

This study describes mobile food vendors (street vendors) in Bronx, NY, considering neighborhood-level correlations with demographic, diet, and diet-related health measures from City data. Vendors offering exclusively "less-healthy" foods (e.g., chips, processed meats, sweets) outnumbered vendors offering exclusively "healthier" foods (e.g., produce, whole grains, nuts). Wet days and winter months reduced all vending on streets, but exclusively "less-healthy" vending most. In summer, exclusively "less-healthy" vending per capita inversely correlated with neighborhood-mean fruit-and-vegetable consumption and directly correlated with neighborhood-mean BMI and prevalences of hypertension and hypercholesterolemia (Spearman correlations 0.90-1.00, p values 0.037 to <0.001). In winter, "less-healthy" vending per capita directly correlated with proportions of Hispanic residents and those living in poverty (Spearman correlations 0.90, p values 0.037). Mobile food vending may contribute negatively to urban food-environment healthfulness overall, but exacerbation of demographic, diet, and diet-related health disparities may vary by weather, season, and neighborhood characteristics., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

In food-environment research, an alternative to resource-intensive direct observation on the ground has been the use of commercial business lists. We sought to determine how well a frequently used commercial business list measures a dense urban food environment like the Bronx, NY. On 155 Bronx street segments, investigators compared two different levels for matches between the business list and direct ground observation: lenient (by business type) and strict (by business name). For each level of matching, researchers calculated sensitivities and positive predictive values (PPVs) for the business list overall and by broad business categories: General Grocers (eg, supermarkets), Specialty Food Stores (eg, produce markets), Restaurants, and Businesses Not Primarily Selling Food (eg, newsstands). Even after cleaning the business list (eg, for cases of multiple listings at a single location), and allowing for inexactness in listed street addresses and spellings of business names, the overall performance of the business list was poor. For strict matches, the business list had an overall sensitivity of 39.3% and PPV of 45.5%. Sensitivities and PPVs by broad business categories were not meaningfully different from overall values, although sensitivity for General Grocers and PPV for Specialty Food Stores were particularly low: 26.2% and 32%, respectively. For lenient matches, sensitivities and PPVs were somewhat higher but still poor: 52.4% to 60% and 60% to 75%, respectively. The business list is inadequate to measure the actual food environment in the Bronx. If results represent performance in other settings, findings from prior studies linking food environments to diet and diet-related health outcomes using such business lists are in question, and future studies of this type should avoid relying solely on such business lists., (Copyright © 2013 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.)

Racial and ethnic disparities in obesity persist despite a narrowing in obesity risk associated with socioeconomic status. The household environment has been shown to be important in understanding obesity-promoting behaviors in diverse populations. Our current study was designed to examine the relationship between household density and obesity in young Black and White adults aged 18-30 years from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort. All sociodemographic and leisure-time physical activity (LTPA) information for this study was collected by questionnaire between 1990-1991. Height was collected using a mounted centimeter ruler. Weight was measured on a balance beam scale. Obesity was defined as a body mass index > or = 30 kg/m2. Household density (HD) was defined as the ratio of people to bedrooms in the home. High HD was defined as a ratio > 1. Bivariate analysis showed that more women tend to live in high density households compared to men (45.4% vs 38.9%; P < .01) and more Blacks tend to live in high density households compared to Whites (53.7% vs 31.8%). Leisure-time physical activity index was lower in Blacks than in Whites (2.5% vs 2.6%; P < .01). Blacks had a higher prevalence of obesity than Whites (27.1% vs 11.8%; P < .01). Logistic regression analysis showed that Black women within high HD were at highest risk for obesity compared to White women living within low HD (OR = 4.88%; 95% CI: 3.56-6.67). HD may provide an important context in understanding racial disparities in obesity-promoting behaviors.

Introduction: Cerebral emboli have been detected during intramedullary orthopaedic procedures. The quantity of emboli produced and their clinical effects are currently not known. This study aimed to quantify the intra-operative cerebral embolic load using transcranial Doppler ultrasound during the intramedullary stabilisation of femoral and tibial diaphyseal fractures. Clinical cognitive function was also assessed after surgery and any relationship to the cerebral embolic load determined., Patients and Methods: Prospective cohort study of 20 patients with femoral or tibial diaphyseal fractures treated with reamed intramedullary nailing. The intra-operative cerebral embolic load was measured using transcranial Doppler ultrasound of the middle meningeal artery. Cognitive function was assessed 3 days after surgery using a range of validated neuropsychological tests. The cognitive results were compared to predicted scores matched for age and intelligence quotient as is the standard method of cognitive assessment after trauma., Results: Four patients had detectable cerebral emboli with counts of only 2, 3, 3, and 9 respectively. A significantly poorer than predicted cognitive score occurred in immediate and delayed memory recall tests. However there was no significant difference in any cognitive function score between those patients who had detectable cerebral emboli and those who did not., Discussion: Small numbers of cerebral emboli were detected during intramedullary stabilisation of lower limb long bone fractures but with no apparent cognitive effect. This poor correlation is similar to recent studies performed on arthroplasty patients and also conforms to the extensive cardiac surgery literature which would indicate that such low levels of systemic embolisation are unlikely to consistently produce cerebral clinical effects.

Objectives: To investigate an increase in the number of Salmonella enteritidis isolates detected in a large hospital to ascertain whether it was due to a nosocomial source, to identify the mechanisms of transmission, and to institute effective control measures to prevent future episodes., Design: Observational study, survey of all microbiological samples positive for S. enteritidis detected in the hospital, outbreak investigation, and review of the literature., Setting: A tertiary-care teaching hospital for adults in Barcelona, Spain., Results: During a 7-month period from May to November 1998, we identified 22 inpatients with S. enteritidis infection for whom nosocomial acquisition was strongly suspected. The attack rate was 0.138 per 1,000 patient-days. All affected patients were immunosuppressed and overall mortality was 41% (9 of 22). A sample of a meal cooked in the kitchen was culture positive for S. enteritidis. All isolates shared the same antibiotic susceptibility pattern and all except one shared the same pulsed-field gel electrophoresis (PFGE) pattern, but PFGE could not differentiate between outbreak-related and control strains. After compliance with kitchen hygiene procedures was emphasized and cleansing was intensified, no more cases were detected., Conclusions: Apparently, sporadic cases of S. enteritidis may be part of an outbreak with a low attack rate. A small but persistent inoculum affecting only individuals with special predisposition for Salmonella infection might account for this. Suspicion should be raised in hospitals and institutions with a highly susceptible population.