Objective. To measure serum levels of tumor necrosis factor a (TNFa) and interleukin-6 (IL-6) in patients with rheumatoid arthritis (RA) and agematched control subjects and to study how these correlate with serum levels of hyaluronan (HA) and antigenic keratan sulfate (KS) and other biochemical as well as clinical indicators of disease activity.Methods. Immunoassays were used to measure levels of TNFa, IL-6, HA, and antigenic KS in the serum of 35 patients with RA and a group of age-and sex-matched control subjects. Clinical disease activity in the RA group was assessed using the Lansbury index. Drug intake was recorded and the erythrocyte sedimentation rate, and levels of fibrinogen, creatinine, biliru-_ _ From the ICP, Connective Tissue Group, and the Department

Most of the filtered glucose is reabsorbed in the early proximal tubule by the sodium-glucose cotransporter SGLT2. The glycosuric effect of the SGLT2 inhibitor ipragliflozin is linked to a diuretic and natriuretic effect that activates compensatory increases in fluid and food intake to stabilize body fluid volume (BFV). However, the compensatory mechanisms that are activated on the level of renal tubules remain unclear. Type 2 diabetic Goto-Kakizaki (GK) rats were treated with vehicle or 0.01% (in diet) ipragliflozin with free access to fluid and food. After 8 weeks, GK rats were placed in metabolic cages for 24-hr. Ipragliflozin decreased body weight, serum glucose and systolic blood pressure, and increased fluid and food intake, urinary glucose and Na + excretion, urine volume, and renal osmolar clearance, as well as urine vasopressin and solute-free water reabsorption (TcH2O). BFV, measured by bioimpedance spectroscopy, and fluid balance were similar among the two groups. Urine vasopressin in ipragliflozin-treated rats was negatively and positively associated with fluid balance and TcH2O, respectively. Ipragliflozin increased the renal membrane protein expression of SGLT2, aquaporin (AQP) 2 phosphorylated at Ser269 and vasopressin V2 receptor. The expression of SGLT1, GLUT2, AQP1, and AQP2 was similar between the groups. In conclusion, the SGLT2 inhibitor ipragliflozin induced a sustained glucosuria, diuresis, and natriuresis, with compensatory increases in fluid intake and vasopressin-induced TcH2O in proportion to the reduced fluid balance to maintain BFV. These results indicate that the osmotic diuresis induced by SGLT2 inhibition stimulates compensatory fluid intake and renal water reabsorption to maintain BFV. K E Y W O R D Sbioimpedance analysis, glucosuria, SGLT2 inhibition, vasopressin, water reabsorption

BACKGROUND Risk factors for delirium are well‐described, yet there is no widely used tool to predict the development of delirium upon admission in hospitalized medical patients. OBJECTIVE To develop and validate a tool to predict the likelihood of developing delirium during hospitalization. DESIGN Prospective cohort study with derivation (May 2010–November 2010) and validation (October 2011–March 2012) cohorts. SETTING Two academic medical centers and 1 Veterans Affairs medical center. PATIENTS Consecutive medical inpatients (209 in the derivation and 165 in the validation cohort) over age 50 years without delirium at the time of admission. MEASUREMENTS Delirium assessed daily for up to 6 days using the Confusion Assessment Method. RESULTS The AWOL prediction rule was derived by assigning 1 point to each of 4 items assessed upon enrollment that were independently associated with the development of delirium (Age ≥ 80 years, failure to spell “World” backward, disOrientation to place, and higher nurse‐rated iLlness severity). Higher scores were associated with higher rates of delirium in the derivation and validation cohorts (P for trend < 0.001 and 0.025, respectively). Rates of delirium according to score in the combined population were: 0(1/50, 2%), 1(5/141, 4%), 2(15/107, 14%), 3(10/50, 20%), and 4(7/11, 64%) (P for trend < 0.001). Area under the receiver operating characteristic curve for the derivation and validation cohorts was 0.81 (0.73–0.90) and 0.69 (0.54–0.83) respectively. CONCLUSIONS The AWOL prediction rule characterizes medical patients' risk for delirium at the time of hospital admission and could be used for clinical stratification and in trials of delirium prevention. Journal of Hospital Medicine 2013;8:493–499. © 2013 Society of Hospital Medicine

The chronic intrinsic diuretic and natriuretic tone of sodium-glucose cotransporter 2 (SGLT2) inhibitors is incompletely understood because their effect on body fluid volume (BFV) has not been fully evaluated and because they often increase food and fluid intake at the same time. Here we first compared the effect of the SGLT2 inhibitor ipragliflozin (Ipra, 0.01% in diet for 8 wk) and vehicle (Veh) in Spontaneously Diabetic Torii rat, a nonobese type 2 diabetic model, and nondiabetic Sprague-Dawley rats. In nondiabetic rats, Ipra increased urinary excretion of Na (UNaV) and fluid (UV) associated with increased food and fluid intake. Diabetes increased these four parameters, but Ipra had no further effect, probably because of its antihyperglycemic effect, such that glucosuria and, as a consequence, food and fluid intake were unchanged. Fluid balance and BFV, determined by bioimpedance spectroscopy, were similar among the four groups. To study the impact of food and fluid intake, nondiabetic rats were treated for 7 days with Veh, Ipra, or Ipra+pair feeding+pair drinking (Pair-Ipra). Pair-Ipra maintained a small increase in UV and UNaV versus Veh despite similar food and fluid intake. Pair-Ipra induced a negative fluid balance and decreased BFV, whereas Ipra or Veh had no significant effect compared with basal values. In conclusion, SGLT2 inhibition induces a sustained diuretic and natriuretic tone. Homeostatic mechanisms are activated to stabilize BFV, including compensatory increases in fluid and food intake.

The morbidity associated with cerebral AVM rupture appeared to be higher in our study than previously reported. Morbidity from AVM rupture should be considered as an important factor, together with variables such as risk of AVM rupture and procedural risk, in determining the optimal treatment strategy for unruptured cerebral AVMs.

No abstract

No abstract

No abstract