A Preoperative Multimarker Approach to Evaluate Acute Kidney Injury After Cardiac Surgery.

OBJECTIVE: To investigate whether a multimarker strategy combining preoperative biomarkers representing distinct pathophysiologic pathways enhances preoperative risk assessment of acute kidney injury after cardiac surgery (CSA-AKI) and increases knowledge of underlying pathogenesis. DESIGN: Prospective, cohort study. SETTING: Single-center tertiary referral hospital. PARTICIPANTS: The study comprised 1,015 adults undergoing cardiac surgery with cardiopulmonary bypass. INTERVENTIONS: CSA-AKI was defined as≥50% increase in serum creatinine concentration, absolute increase≥26 µmol/L, or new requirement for dialysis. Preoperative and perioperative information until hospital discharge was recorded. Preoperative plasma levels of C-reactive protein, terminal complement complex, neopterin, lactoferrin, N-terminal pro-brain natriuretic peptide, and cystatin C were determined using enzyme immunoassays. Biomarkers were selected based on causal hypotheses of underlying mechanisms and were related to inflammatory, hemodynamic, or renal signaling pathways. MEASUREMENTS AND MAIN RESULTS: One hundred patients (9.9%) developed CSA-AKI. Higher baseline plasma concentrations of neopterin and N-terminal pro-brain natriuretic peptide were associated independently with CSA-AKI (p = 0.04 and p<0.001, respectively). Lower baseline plasma lactoferrin concentrations were observed in patients with CSA-AKI (p = 0.05). Compared with clinical risk assessment, addition of these biomarkers provided a slight, but significant, increment in predictive utility (area under the curve 0.81-0.83, likelihood ratio test p<0.001). A net of 12% of patients were reclassified correctly, and improved prediction was demonstrated, especially in patients with intermediate risk (56% correct reclassification). CONCLUSIONS: Preoperative hemodynamic, renal, and immunologic function play central roles in the pathogenesis of CSA-AKI. These findings add evidence to the potential of a multimarker approach to improve preoperative prediction of CSA-AKI.

The Hippo signaling pathway is required for salivary gland development and its dysregulation is associated with Sjogren's syndrome.

Sjogren's syndrome (SS) is a complex autoimmune disease that primarily affects salivary and lacrimal glands and is associated with high morbidity. Although the prevailing dogma is that immune system pathology drives SS, increasing evidence points to structural defects, including defective E-cadherin adhesion, to be involved in its etiology. We have shown that E-cadherin has pivotal roles in the development of the mouse salivary submandibular gland (SMG) by organizing apical-basal polarity in acinar and ductal progenitors and by signaling survival for differentiating duct cells. Recently, E-cadherin junctions have been shown to interact with effectors of the Hippo signaling pathway, a core pathway regulating the organ size, cell proliferation, and differentiation. We now show that Hippo signaling is required for SMG-branching morphogenesis and is involved in the pathophysiology of SS. During SMG development, a Hippo pathway effector, TAZ, becomes increasingly phosphorylated and associated with E-cadherin and α-catenin, consistent with the activation of Hippo signaling. Inhibition of Lats2, an upstream kinase that promotes TAZ phosphorylation, results in dysmorphogenesis of the SMG and impaired duct formation. SMGs from non-obese diabetic mice, a mouse model for SS, phenocopy the Lats2-inhibited SMGs and exhibit a reduction in E-cadherin junctional components, including TAZ. Importantly, labial specimens from human SS patients display mislocalization of TAZ from junctional regions to the nucleus, coincident with accumulation of extracellular matrix components, fibronectin and connective tissue growth factor, known downstream targets of TAZ. Our studies show that Hippo signaling has a crucial role in SMG-branching morphogenesis and provide evidence that defects in this pathway are associated with SS in humans.

Oral distress in primary Sjögren's syndrome: implications for health-related quality of life.

The aims of the study were to evaluate oral distress in patients with primary Sjögren's syndrome (pSS) compared with age- and sex-matched Norwegian normative data, to estimate the occurrence of oral symptoms in pSS, and to evaluate the impact of oral distress on health-related quality of life (HRQoL). The Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) was used to assess HRQoL, and the Oral Health Impact Profile 14 (OHIP-14) was used to measure oral distress. Of the 246 pSS patients invited to participate in the study, 177 (72%) responded. Data were analysed for the female participants (n = 163). Significant deviations from normative estimates were found in all OHIP-14 item results, and the findings indicated a high level of oral distress among the pSS patients. Health-related quality of life was decreased among pSS patients, with the largest deviations from normative estimates related to general health and role physical. The patients with high levels of oral distress scored significantly lower than patients with low levels of oral distress in five of the SF-36 subscales, indicating that oral conditions have a marked impact on general quality of life. In conclusion, oral distress in pSS is pronounced and severe, and should receive increased attention with a view to improving the quality of life for these patients.