Biofilm infections can induce chronic inflammation and stall the normal orchestrated course of wound-healing cascades. Herein, pH-switchable antimicrobial hydrogel with nanofiber networks for biofilm eradication and rescuing stalled healing in chronic wounds is reported on the basis of the self-assembly of a designed octapeptide (IKFQFHFD) at neutral pH. This hydrogel is biocompatible and exhibits an acidic pH (pathological environment of infected chronic wounds)-switchable broad-spectrum antimicrobial effect via a mechanism involving cell wall and membrane disruption. The antimicrobial activity of hydrogel is derived from its acidic pH-dependent nanofiber network destabilization and activated release of IKFQFHFD, which is antimicrobial only at acidic pH due to the antimicrobial peptide-like molecular structure. In addition, supramolecular nanofiber networks loaded with drugs of cypate (photothermal agent) and proline (procollagen component) are further developed. In vitro experiments show that loaded drugs exhibit acidic pH (pH ∼ 5.5)-responsive release profiles, and synergistic biofilm eradication and subsequent healing cascade activation of cells proliferation are achieved on the basis of the supramolecular nanofiber networks. Remarkably, the nanofiber networks of hydrogel enable in vivo complete healing of MRSA biofilm infected wound in diabetic mice within 20 days, showing great potential as promising chronic wound dressings. The proposed synergistic strategy for eradicating biofilm and activating subsequent healing cascades may offer a powerful modality for the management of clinical chronic wounds.

Patients with cirrhosis are susceptible to bacterial infection, which can result in circulatory dysfunction, renal failure, hepatic encephalopathy, and a decreased survival rate. Severe sepsis is frequently associated with adrenal insufficiency, which may lead to hemodynamic instabity and a poor prognosis. We evaluated adrenal function using short corticotropin stimulation test (SST) in 101 critically ill patients with cirrhosis and severe sepsis. Adrenal insufficiency occurred in 51.48% of patients. The patients with adrenal insufficiency had a higher hospital mortality rate when compared with those with normal adrenal function (80.76% vs. 36.7%, P < .001). The cumulative rates of survival at 90 days were 15.3% and 63.2% for the adrenal insufficiency and normal adrenal function groups, respectively (P < .0001). The hospital survivors had a higher cortisol response to corticotropin (16.2 ؎ 8.0 vs. 8.5 ؎ 5.9 g/dL, P < .001). The cortisol response to corticotropin was inversely correlated with various disease severity, Model for End-Stage Liver Disease, and Child-Pugh scores. Acute physiology, age, chronic health evaluation III score, and cortisol increment were independent factors to predict hospital mortality. Mean arterial pressure on the day of SST was lower in patients with adrenal insufficiency (60 ؎ 14 vs. 74.5 ؎ 13 mm Hg, P < .001 ), and a higher proportion of these patients required vasopressors (73% vs. 24.48%, P < .001). Mean arterial pressure, serum bilirubin, vasopressor dependency, and bacteremia were independent factors that predicted adrenal insufficiency. In conclusion, adrenal insufficiency is common in critically ill patients with cirrhosis and severe sepsis. It is related to functional liver reserve and disease severity and is associated with hemodynamic instability, renal dysfunction, and increased mortality. (HEPATOLOGY 2006;43:673-681.) C ritical illness is accompanied by the activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is highlighted by increased serum corticotropin and cortisol levels. [1][2][3] The activation of the HPA axis is a crucial component of the host's adaptation to severe stress. Cortisol is essential for the normal function of the immune system, maintenance of vascular tone, and various cellular functions. In patients with severe sepsis, the integrity of the HPA axis can be impaired by a variety of mechanisms. 1,4 Recently, the concept of relative adrenal insufficiency has been used to describe a subnormal adrenal response to adrenocorticotropin in severe illness, in which the cortisol levels, even though high in terms of absolute value, are inadequate to control the inflammatory situation. 1 The short corticotropin stimulation test (SST) is most commonly used to evaluate the appropriateness of the adrenal response in this setting. In patients with septic shock, a decreased response to the SST, namely, an absolute increment of the serum cortisol level less than 9 g/dL, is associated with an impaired vascular reactivity to vasopressors 5 and a high mortalit...

Sensitive and quantitative assessment of changes in circulating tumor cells (CTCs) can help in cancer prognosis and in the evaluation of therapeutics efficacy. However, extremely low occurrence of CTCs in the peripheral blood (approximately one CTC per billion blood cells) and potential changes in molecular biomarkers during the process of epithelial to mesenchymal transition (EMT) create technical hurdles to the enrichment and enumeration CTCs. Recently, efforts have been directed toward development of antibody-capture assays based on the expression of the common biomarker - the epithelial cell adhesion molecule (EpCAM) of epithelium-derived cancer cells. Despite some promising results, the assays relying on EpCAM capture have shown inconsistent sensitivity in clinical settings and often fail to detect CTCs in patients with metastatic cancer. We have addressed this problem by the development of an assay based on hybrid magnetic/plasmonic nanocarriers and a microfluidic channel. In this assay cancer cells are specifically targeted by antibody-conjugated magnetic nanocarriers and are separated from normal blood cells by a magnetic force in a microfluidic chamber. Subsequently, immunofluorescence staining is used to differentiate CTCs from normal blood cells. We demonstrated in cell models of colon, breast and skin cancers that this platform can be easily adapted to a variety of biomarkers, targeting both surface receptor molecules and intracellular biomarkers of epithelial-derived cancer cells. Experiments in whole blood showed capture efficiency greater than 90% when two cancer biomarkers are used for cell capture. Thus, the combination of immunotargeted magnetic nanocarriers with microfluidics provides an important platform that can improve the effectiveness of current CTC assays by overcoming the problem of heterogeneity of tumor cells in the circulation.

The clinicopathological significance of colorectal mucinous carcinoma is controversial, although some authors feel mucinous carcinoma has a worse prognosis than that of non-mucinous carcinoma. To clarify the significance of this type of carcinoma in Taiwan, a retrospective review of patients with colorectal carcinoma treated at Chang Gung Memorial Hospital between 1984 and 1988 was undertaken. During this period, 53 mucinous carcinomas and 401 non-mucinous carcinomas fulfilling the inclusion criteria were analysed. Mucinous carcinomas were more common in patients 39 years of age or under (P < 0.005). Most mucinous carcinomas were located in the rectum/rectosigmoid, followed by the right colon; however, the right colon had a higher relative incidence (38 vs 8%, respectively; P < 0.005). Mucinous carcinomas presented at a significantly more advanced stage (23 vs 8%, respectively, stage D disease; P < 0.005) and had a markedly lower curative resection rate (68 vs 84%, respectively; P < 0.05). Following curative resection, mucinous carcinomas tended to have an increased incidence of subsequent distant metastasis (27.8 vs 18.8%, respectively; P < 0.005). The overall survival rate of patients with mucinous carcinoma was worse than that of non-mucinous carcinoma (P < 0.005). Multivariate analysis showed that clinically important predictive factors were stage of disease on diagnosis and subsequent distant metastasis. The mucinous histological type itself was not an independent prognostic factor in colorectal cancer.