Despite the recent decline in mortality from coronary heart disease (CHD), this disease remains the leading killer of US adults of all ages. CHD in young adults is not as well characterized as CHD in older individuals because it occurs less frequently, but this disease can have devastating consequences for young patients and their families. As in older adults, the majority of coronary events in young adults are related to atherosclerosis, and one or more of the traditional CHD risk factors is typically present. Young patients, however, are more likely than older patients to be smokers, male, obese, and to have a positive family history. Risk factor reduction is thus of major importance in managing young CHD patients. Approximately 20% of CHD in young adults, however, is related to non-atherosclerotic factors, such as coronary abnormalities, connective tissue disorders, and autoimmune diseases. Cocaine and other illicit drug use have been increasingly associated with acute myocardial infarction and accelerated atherosclerosis. The differences in etiologies and risk profiles of younger and older CHD patients result in differences in disease progression, prognosis, and treatment. Limited data suggest that prognosis may be better in the young population, although long-term mortality studies have suggested otherwise. Screening for CHD in the young population may help to improve prognosis in young patients by detecting subclinical disease, although more studies are necessary to establish reference limits for this young population. Additional research must also focus on treatment concerns that are specific to young patients.

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CXCR4 regulates hematopoietic and tumor cell homing to bone, but its role during osteoclast (OC) development is unknown. We investigated the role of CXCR4 in osteoclastogenesis and in a model of bone metastasis. Compared with controls, mice reconstituted with CXCR4 null hematopoietic cells exhibited elevated markers of bone resorption, increased OC perimeter along bone, and increased bone loss. CXCR4؊/؊ OCs demonstrated accelerated differentiation and enhanced bone resorption in vitro. Furthermore, tumor growth specifically in bone was significantly increased in mice reconstituted with CXCR4؊/؊ hematopoietic cells. Finally, enhancement of bone tumor growth in the absence of CXCR4 was abrogated with the OC inhibitor, zoledronic acid. These data demonstrate that disruption of CXCR4 enhances osteoclastogenesis and suggest that inhibition of CXCR4 may enhance established skeletal tumor burden by increasing OC activity.bone metastasis ͉ osteoclast B one metastases are a significant cause of morbidity, causing pain, pathologic fractures, spinal cord compression, and hypercalcemia (1). Tumor cells that reach the bone marrow (BM) can stimulate one or both types of cells involved in bone remodeling, namely osteoblasts (stromal cell origin) or osteoclasts (OCs) (hematopoietic cell lineage), leading to new bone formation and osteoblastic lesions or bone loss and osteolytic lesions, respectively. OC resorption releases bone matrix-derived growth factors that can enhance local tumor growth (1-3). Disruption of OC resorption can decrease tumor growth in bone (3), and we have recently shown that pharmacologic enhancement of OC activity with granulocyte-colony stimulating factor increases tumor growth in bone in mice (4).CXCR4 is a seven-transmembrane G protein-coupled receptor expressed by many cell types, including hematopoietic, endothelial, stromal, and neuronal cells (5). Stromal cell-derived factor-1 (SDF-1) (or CXCL12) is the only known ligand for CXCR4 and is produced by multiple BM cell types, including stromal cells, osteoblasts, and OCs (6-8). CXCR4/SDF-1 are critical molecules in the process of hematopoietic stem cell (HSC) homing to and egress from the BM (9, 10). Gene-targeted disruptions of CXCR4 and SDF-1 are embryonic lethal, but examination of late-stage embryos reveal diminished HSC homing to the fetal BM (11-13). Additionally, inhibitors of either SDF-1 or CXCR4 have been shown to impair BM engraftment in transplant models (5). Small molecule inhibitors of CXCR4 mobilize HSCs and progenitor cells from the BM into the peripheral blood. Clinical trials are underway using CXCR4 inhibitors to mobilize and collect HSCs/hematopoietic progenitor cells from the peripheral blood in preparation for stem cell transplantation for malignant BM diseases (14).Signaling through CXCR4 has been shown to have both stimulatory and inhibitory roles on various hematopoietic cells, including promoting survival and proliferation of HSCs (5), inducing apoptosis in T cells (15), or causing quiescence in neural progenitors (16). The s...

In an analysis of the Acute Liver Failure Study Group cohort, we found acetaminophen-induced ALI and ALF to be more common among women. Women have greater critical care needs than men, and increased risk for severe HE, which could be due in part to increased use of sedatives. Future studies should investigate sex differences in acetaminophen metabolism and hepatotoxicity, particularly among users of opioids.

Background & Aims: Gender disparities exist in outcomes among patients with cirrhosis. We sought to evaluate the role of gender on hospital course and in-hospital outcomes in patients with cirrhosis to help better understand these disparities. Study:We analyzed data from the National Inpatient Sample (NIS), years 2009-2013, to identify patients with any diagnosis of cirrhosis. We calculated demographic and clinical characteristics by gender, as well as cirrhosis complications. Our primary outcome was inpatient mortality. We used logistic regression to associate baseline characteristics and cirrhosis complications with inpatient mortality.Results: Our cohort included 553,017 patients with cirrhosis admitted from 2009-2013. Women made up 39% of the cohort; median age was 57 with 66% non-Hispanic White. Women were more likely than men to have non-cirrhosis comorbidities, including diabetes and hypertension, but were less likely to have most cirrhosis complications, including ascites and variceal bleeding. Women were more likely than men to have acute bacterial infections (34.9% vs 28.2%, p < 0.001), and were less likely than men to die in the hospital on univariable (OR 0.88, 95% CI 0.86 -0.90, p < 0.001) and multivariable (OR 0.86, 95% CI 0.83 -0.88, p < 0.001) analysis. Conclusions:In patients hospitalized with cirrhosis, women have lower rates of hepatic decompensating events and higher rates of non-hepatic comorbidities and infections, resulting in lower in-hospital mortality. Understanding differences in indications for and disposition following hospitalization may help with the development of gender-specific cirrhosis management programs to improve long-term outcomes in women and men living with cirrhosis.