Involvement of nuclear NHERF1 in colorectal cancer progression.

NHERF1 (Na+/H+ exchanger regulatory factor 1) is expressed in the luminal membrane of many epithelia, and associated with proteins involved in tumor progression. Alterations of NHERF1 expression in different sites of metastatic colorectal cancer (mCRC) suggest a dynamic role of this protein in colon carcinogenesis. We focused on the observation of the altered expression of NHERF1 from non-neoplastic tissues to metastatic sites by immunohistochemistry. Moreover, we studied, by immunofluorescence, the colocalization between NHERF1 and the epidermal growth factor receptor (EGFR), whose overexpression is implicated in CRC progression. NHERF1 showed a different localization and expression in the examined sites. The distant non-neoplastic tissues showed NHERF1 mostly expressed at the apical membrane, while in surrounding non-neoplastic tissue decreased the apical membrane and increased cytoplasmic immunoreactivity. In adenomas a shift from apical membrane to cytoplasmic localization and nuclear expression were observed. Cytoplasmic staining in the tumor, and metastatic sites was stronger than surrounding non-neoplastic tissue. Furthermore, nuclear NHERF1 expression was noted in 80% of all samples and surprisingly, it appeared already in adenoma lesions, suggesting that NHERF1 represents an early marker of pre-morphological triggering of colorectal carcinogenesis. Then, in few tumors a positive direct correlation between membrane NHERF1 and EGFR expression was evidenced by their colocalization. Nuclear NHERF1 expression, present in the early stages of carcinogenesis and related with poor prognosis, may contribute to the onset of malignant phenotype. Specifically, we hypothesize the direct involvement of nuclear NHERF1 in both carcinogenesis and progression and its role as a potential colorectal cancer marker.

The nephro-geriatric unit in a lean-oriented in-hospital model of care.

Nephrologists worldwide are gradually coping with elderly patients. This is because of the burden of chronic disease in the aging population and specifically chronic kidney disease (CKD). CKD in the elderly rarely occurs in isolation from other chronic conditions and can often be a marker of these conditions themselves. Geriatricians usually take care of chronic conditions and are trained to perform comprehensive geriatric assessment, a tool to estimate frailty, that is the risk of adverse outcome, disability, and death in the clinical setting of elderly inpatients. Unfortunately, they are not used to a CHD invasive and non-invasive approach and so there is no doubt about the need for a co-managed care model for these patients. However, where and how this model must be realized is still questionable. New hospital care models are patient-centered and encompass the concepts of departments to embrace the differentiated levels of care approach. According to this model the hospital is subdivided into three different standards of care: 1-high; 2 -intermediate; 3- low and this organization avoids inpatients being transferred frequently to different units, receiving specific care easily obtained by moving and changing the medical staff in charge of the patient. The lean care approach integrates the principles of the Toyota Producing System (TPS), a leading system of the industrial world, into intensity-based hospital care, thereby maximizing quality processes and promoting co-managed care as in the nephro-geriatric clinical setting.