Kiyohide Fushimi

Updating and Validating the Charlson Comorbidity Index and Score for Risk Adjustment in Hospital Discharge Abstracts Using Data From 6 Countries

With advances in the effectiveness of treatment and disease management, the contribution of chronic comorbid diseases (comorbidities) found within the Charlson comorbidity index to mortality is likely to have changed since development of the index in 1984. The authors reevaluated the Charlson index and reassigned weights to each condition by identifying and following patients to observe mortality within 1 year after hospital discharge. They applied the updated index and weights to hospital discharge data from 6 countries and tested for their ability to predict in-hospital mortality. Compared with the original Charlson weights, weights generated from the Calgary, Alberta, Canada, data (2004) were 0 for 5 comorbidities, decreased for 3 comorbidities, increased for 4 comorbidities, and did not change for 5 comorbidities. The C statistics for discriminating in-hospital mortality between the new score generated from the 12 comorbidities and the Charlson score were 0.825 (new) and 0.808 (old), respectively, in Australian data (2008), 0.828 and 0.825 in Canadian data (2008), 0.878 and 0.882 in French data (2004), 0.727 and 0.723 in Japanese data (2008), 0.831 and 0.836 in New Zealand data (2008), and 0.869 and 0.876 in Swiss data (2008). The updated index of 12 comorbidities showed good-to-excellent discrimination in predicting in-hospital mortality in data from 6 countries and may be more appropriate for use with more recent administrative data.

Urinary Excretion of Aquaporin-2 in Patients with Diabetes Insipidus

BACKGROUND Urine-concentrating ability is regulated by vasopressin. Recently, the specific water-channel protein of the renal collecting duct, known as aquaporin-2, was cloned. However, it is not certain whether this molecule is responsive to vasopressin. METHODS We measured the urinary excretion of aquaporin-2 and its response to vasopressin in 11 normal subjects and 9 patients with central or nephrogenic diabetes insipidus. The urine samples were collected during periods of dehydration and hydration and after the administration of vasopressin. Urine samples were analyzed for aquaporin-2 by the Western blot assay and immunogold labeling, and the amount of aquaporin-2 was determined by radioimmunoassay. RESULTS Aquaporin-2 was detectable in the urine in both soluble and membrane-bound forms. In the five normal subjects tested, the mean (+/- SE) urinary excretion of aquaporin-2 was 11.2 +/- 2.2 pmol per milligram of creatinine after a period of dehydration, and it decreased to 3.9 +/- 1.9 pmol per milligram of creatinine (P = 0.03) during the second hour after a period of hydration. In the six other normal subjects, an infusion of desmopressin (1-desamino-8-D-arginine vasopressin) increased the urinary excretion of aquaporin-2 from 0.8 +/- 0.3 to 11.2 +/- 1.6 pmol per milligram of creatinine (P < 0.001). The five patients with central diabetes insipidus also had increases in urinary excretion of aquaporin-2 in response to the administration of vasopressin, but the four patients with X-linked or non-X-linked nephrogenic diabetes insipidus did not. CONCLUSIONS Aquaporin-2 is detectable in the urine, and changes in the urinary excretion of this protein can be used as an index of the action of vasopressin on the kidney.

Cloning, characterization, and chromosomal mapping of human aquaporin of collecting duct.

We recently cloned a cDNA of the collecting duct apical membrane water channel of rat kidney, which is important for the formation of concentrated urine (Fushima, K., S. Uchida, Y. Hara, Y. Hirata, F. Marumo, and S. Sasaki. 1993. Nature [Lond.]. 361:549-552). Since urine concentrating ability varies among mammalian species, we examined whether an homologous protein is present in human kidney. By screening a human kidney cDNA library, we isolated a cDNA clone, designated human aquaporin of collecting duct (hAQP-CD), that encodes a 271-amino acid protein with 91% identity to rat AQP-CD. mRNA expression of hAQP-CD was predominant in the kidney medulla compared with the cortex, immunohistochemical staining of hAQP-CD was observed only in the collecting duct cells, and the staining was dominant in the apical domain. Functional expression study in Xenopus oocytes confirmed that hAQP-CD worked as a water channel. Western blot analysis of human kidney medulla indicated that the molecular mass of hAQP-CD is 29 kD, which is the same mass expected from the amino acid sequence. Chromosomal mapping of the hAQP-CD gene assigned its location to chromosome 12q13. These results could be important for future studies of the pathophysiology of human urinary concentration mechanisms in normal and abnormal states.

Expression and distribution of aquaporin of collecting duct are regulated by vasopressin V2 receptor in rat kidney.

To examine whether expression and distribution of aquaporin of collecting duct (AQP-CD) are regulated by vasopressin V2 receptor (V2R), we performed immunohistochemical studies with specific antibody against AQP-CD. Normal Wistar rats were divided into four groups and treated for 3 d; control, dehydration, vasopressin V1 receptor (V1R) antagonist (OPC-21268 120 mg/kg), V2R antagonist (OPC-31260 30 mg/kg). At time of death, urine osmolality (Uosm) in the dehydration group (1884 +/- 245 mOsm/kg) was significantly higher than that in the control (938 +/- 91). In the V2R antagonist group, Uosm was significantly decreased to 249 +/- 29, whereas V1R antagonist showed no effect on Uosm. In the control and V1R antagonist groups, immunofluorescence studies showed the AQP-CD staining of both apical membrane and subapical cytoplasm of CD cells of the cortex and the inner medulla. Dehydration increased the immunostaining of both apical membrane and subapical cytoplasm of CD cells of the inner medulla, and the degree of increase was dominant in apical membrane. In the V2R antagonist group, only faint staining of apical membrane and weak labeling of cytoplasm of CD cells of the inner medulla were observed. These changes in the localization and protein amount of AQP-CD by dehydration and V2R antagonist were quantitatively confirmed by immunogold studies and immunoblot analysis of the inner medulla. The present results indicate that the distribution and amount of AQP-CD in the CD cells are regulated by vasopressin V2 receptor.

Cross-national comparative performance of three versions of the ICD-10 Charlson index.

Objective:The Charlson comorbidity index has been widely used for risk adjustment in outcome studies using administrative health data. Recently, 3 International Statistical Classification of Diseases, Tenth Revision (ICD-10) translations have been published for the Charlson comorbidities. This study was conducted to compare the predictive performance of these versions (the Halfon, Sundararajan, and Quan versions) of the ICD-10 coding algorithms using data from 4 countries. Methods:Data from Australia (N = 2000–2001, max 25 diagnosis codes), Canada (N = 2002–2003, max 16 diagnosis codes), Switzerland (N = 1999–2001, unlimited number of diagnosis codes), and Japan (N = 2003, max 11 diagnosis codes) were analyzed. Only the first admission for patients age 18 years and older, with a length of stay of ≥2 days was included. For each algorithm, 2 logistic regression models were fitted with hospital mortality as the outcome and the Charlson individual comorbidities or the Charlson index score as independent variables. The c-statistic (representing the area under the receiver operating characteristic curve) and its 95% probability bootstrap distribution were employed to evaluate model performance. Results:Overall, within each populations data, the distribution of comorbidity level categories was similar across the 3 translations. The Quan version produced slightly higher median c-statistics than the Halfon or Sundararajan versions in all datasets. For example, in Japanese data, the median c-statistics were 0.712 (Quan), 0.709 (Sundararajan), and 0.694 (Halfon) using individual comorbidity coefficients. In general, the probability distributions between the Quan and the Sundararajan versions overlapped, whereas those between the Quan and the Halfon version did not. Conclusions:Our analyses show that all of the ICD-10 versions of the Charlson algorithm performed satisfactorily (c-statistics 0.70–0.86), with the Quan version showing a trend toward outperforming the other versions in all data sets.

Antithrombin and mortality in severe pneumonia patients with sepsis-associated disseminated intravascular coagulation: an observational nationwide study

The association between antithrombin use and mortality in patients with sepsis‐associated disseminated intravascular coagulation (DIC) remains controversial.

Impact of hospital volume on hospital mortality, length of stay and total costs after pancreaticoduodenectomy

High morbidity and mortality rates after pancreaticoduodenectomy (PD) have led to concentration of this surgery in high‐volume centres, with improved outcomes. The extent to which better outcomes might be apparent in a healthcare system where the mortality rate is already low is unclear.

Outcomes after laparoscopic or open distal gastrectomy for early-stage gastric cancer: a propensity-matched analysis.

Objective:In a large nationwide administrative database of hospitalized patients, we investigated postoperative outcomes after laparoscopic or open distal gastrectomy in Japan. Background:The benefits of laparoscopic gastrectomy, such as decreased length of stay and morbidity, have typically been evaluated only with limited data on the basis of small samples. Methods:Using the Japanese Diagnosis Procedure Combination Database, we identified 9388 patients who were preoperatively diagnosed with stage I and II gastric cancer and underwent laparoscopic (n = 3937) or open (n = 5451) distal gastrectomy between July and December 2010. One-to-one propensity score matching was performed to compare in-hospital mortality, postoperative complication rates, length of stay, total costs, and 30-day readmission rates between the 2 groups. Results:Patients with younger age, lower comorbidity index, or stage I cancer were more likely to receive laparoscopic gastrectomy. In the propensity-matched analysis with 2473 pairs, the laparoscopic gastrectomy group in comparison with the open gastrectomy group showed a slight reduction in median postoperative length of stay (13 days vs 15 days, P < 0.001) but a slight increase in median total costs (US

Low-dose corticosteroid use and mortality in severe community-acquired pneumonia patients

21,510 vs

Postoperative polymyxin B hemoperfusion and mortality in patients with abdominal septic shock: a propensity-matched analysis.

21,024, P = 0.002). There were no significant differences in in-hospital mortality (0.36% vs 0.28%, P = 0.80), overall postoperative complications (12.9% vs 12.6%, P = 0.73), or 30-day readmission rates (3.2% vs 3.2%, P = 0.94). Conclusions:In this large nationwide cohort of patients with early-stage gastric cancer, laparoscopic gastrectomy was associated with a statistically significant but slight reduction in postoperative length of stay, but no differences between laparoscopic gastrectomy and open gastrectomy were detected in terms of early mortality and morbidity.