Citations

ABSTRACTWe describe a thymidine-dependent small-colony variant ofStaphylococcus aureusassociated with left ventricular assist device infection and prosthetic valve and pacemaker endocarditis.

PurposeAlthough the importance of obesity in colon cancer risk and outcome is recognized, the association of body mass index (BMI) with DNA mismatch repair (MMR) status is unknown.Patients and MethodsBMI (kg/m2) was determined in patients with TNM stage II or III colon carcinomas (n = 2,693) who participated in randomized trials of adjuvant chemotherapy. The association of BMI with MMR status and survival was analyzed by logistic regression and Cox models, respectively.ResultsOverall, 427 (16%) tumors showed deficient MMR (dMMR), and 630 patients (23%) were obese (BMI ≥ 30 kg/m2). Obesity was significantly associated with younger age (P = .021), distal tumor site (P = .012), and a lower rate of dMMR tumors (10% v 17%; P < .001) compared with normal weight. Obesity remained associated with lower rates of dMMR (odds ratio, 0.57; 95% CI, 0.41 to 0.79; P < .001) after adjusting for tumor site, stage, sex, and age. Among obese patients, rates of dMMR were lower in men compared with women (8% v 13%; P = .041). Obesity was associated with higher recurrence rates (P = .0034) and independently predicted worse disease-free survival (DFS; hazard ratio [HR], 1.37; 95% CI, 1.14 to 1.64; P = .0010) and overall survival (OS), whereas dMMR predicted better DFS (HR, 0.59; 95% CI, 0.47 to 0.74; P < .001) and OS. The favorable prognosis of dMMR was maintained in obese patients.ConclusionColon cancers from obese patients are less likely to show dMMR, suggesting obesity-related differences in the pathogenesis of colon cancer. Although obesity was independently associated with adverse outcome, the favorable prognostic impact of dMMR was maintained among obese patients.

Background— Hematopoiesis originates from the dorsal aorta during embryogenesis. Although adult blood vessels harbor progenitor populations for endothelial and smooth muscle cells, it is not known if they contain hematopoietic progenitor or stem cells. Here, we hypothesized that the arterial wall is a source of hematopoietic progenitor and stem cells in postnatal life. Methods and Results— Single-cell aortic disaggregates were prepared from adult chow-fed C57BL/6 and apolipoprotein E–null (ApoE −/− ) mice. In short- and long-term methylcellulose-based culture, aortic cells generated a broad spectrum of multipotent and lineage-specific hematopoietic colony-forming units, with a preponderance of macrophage colony-forming units. This clonogenicity was higher in lesion-free ApoE −/− mice and localized primarily to stem cell antigen-1–positive cells in the adventitia. Expression of stem cell antigen-1 in the aorta colocalized with canonical hematopoietic stem cell markers, as well as CD45 and mature leukocyte antigens. Adoptive transfer of labeled aortic cells from green fluorescent protein transgenic donors to irradiated C57BL/6 recipients confirmed the content of rare hematopoietic stem cells (1 per 4 000 000 cells) capable of self-renewal and durable, low-level reconstitution of leukocytes. Moreover, the predominance of long-term macrophage precursors was evident by late recovery of green fluorescent protein–positive colonies from recipient bone marrow and spleen that were exclusively macrophage colony-forming units. Although trafficking from bone marrow was shown to replenish some of the hematopoietic potential of the aorta after irradiation, the majority of macrophage precursors appeared to arise locally, suggesting long-term residence in the vessel wall. Conclusions— The postnatal murine aorta contains rare multipotent hematopoietic progenitor/stem cells and is selectively enriched with stem cell antigen-1–positive monocyte/macrophage precursors. These populations may represent novel, local vascular sources of inflammatory cells.

Background and Purpose— Patients with aneurysmal subarachnoid hemorrhage are typically kept in the intensive care unit to be monitored for signs of delayed cerebral ischemia (DCI). Identifying patients at lower risk for DCI could have a positive financial impact by allowing earlier transfer from the intensive care unit. Methods— We analyzed 307 consecutive patients admitted to the intensive care unit. Demographic, clinical, and neuroimaging data were recorded. The relationship with absent DCI was analyzed using univariate and multivariate logistic regression models. Results— DCI did not develop in 169 patients (57.9%). Among factors at admission, age 68 years or older ( P =0.0003; OR, 3.16; 95% CI, 1.66–6.39), World Federation of Neurological Surgeons (WFNS) I to III at presentation ( P =0.0003; OR, 2.73; 95% CI, 1.57–4.79), WFNS I to III at worst ( P =0.0003; OR, 2.39; 95% CI, 1.48–3.87), WFNS I to III after resuscitation ( P =0.0006; OR, 2.85; 95% CI, 1.56–5.32), modified Fisher grade 1 to 2 ( P =0.0021; OR, 2.43; 95% CI, 1.37–4.47), absence of intracranial hematoma ( P =0.0042; OR, 2.26; 95% CI, 1.29–4.01), and aneurysm in the posterior circulation ( P =0.025; OR, 1.74; 95% CI, 1.07–2.87) were associated with absence of DCI. On multivariate analysis, a model including age 68 years or older, WFNS I to III at presentation and a modified Fisher grade 1 to 2 were independently predictive of the absence of DCI, with a specificity of 100% and a positive predictive value of 100%. Conclusions— We propose a new model that can reliably identify patients with aneurysmal subarachnoid hemorrhage who are at very low risk for DCI. These patients could be candidates for early transfer to the general ward.

Background and Purpose— It is important to know the costs for hospitalization for ischemic stroke patients treated with intravenous thrombolysis so that comparisons can be made with payments to hospitals. Methods— Using the National Inpatient Sample, we evaluated hospitalization costs for patients treated with intravenous thrombolysis for acute ischemic stroke in the United States from 2001 to 2008. Cost data were correlated with demographics and clinical outcome. Results— Intravenous thrombolysis for acute ischemic stroke was received by 63 472 patients; 24 094 patients were younger than age 65 years and 40 780 patients were 65 years or older. Median hospital costs in 2008 dollars were $14 102 (interquartile range, $9987–$20 819) for patients with good outcome, $18 856 (interquartile range, $13 145–$30 423) for patients with severe disability, and $19 129 (interquartile range, $11 966–$30 781) for patients with in-hospital mortality. Average 2008 Medicare payments were $10 098 for intravenous thrombolysis without complication and $13 835 for intravenous thrombolysis with major complication. Conclusions— Hospitalization costs for patients treated with intravenous thrombolysis are substantially higher than Medicare payments.

Abstract Innate immunity provides the first line of response to invading pathogens and a variety of environmental insults. Recent studies identified novel subsets of innate lymphoid cells that are capable of mediating immune responses in mucosal organs. In this paper, we describe a subset of lymphoid cells that is involved in innate type 2 immunity in the lungs. Airway exposure of naive BALB/c or C57BL/6J mice to IL-33 results in a rapid (&lt;12 h) production of IL-5 and IL-13 and marked airway eosinophilia independently of adaptive immunity. In the lungs of nonsensitized naive mice, IL-33–responsive cells were identified that have a lymphoid morphology, lack lineage markers, highly express CD25, CD44, Thy1.2, ICOS, Sca-1, and IL-7Rα (i.e., Lin−CD25+CD44hi lymphoid cells), and require IL-7Rα for their development. Airway exposure of naive mice to a clinically relevant ubiquitous fungal allergen, Alternaria alternata, increases bronchoalveolar lavage levels of IL-33, followed by IL-5 and IL-13 production and airway eosinophilia without T or B cells. This innate type 2 response to the allergen is nearly abolished in mice deficient in IL-33R (i.e., ST2), and the Lin−CD25+CD44hi lymphoid cells in the lungs are required and sufficient to mediate the response. Thus, a subset of innate immune cells that responds to IL-33 and vigorously produces Th2-type cytokines is present in mouse lungs. These cells may provide a novel mechanism for type 2 immunity in the airways and induction of allergic airway diseases such as asthma.