Structural comparison of RdgC with other ring-shaped DNA-binding proteins

<p><b>Copyright information:</b></p><p>Taken from "The recombination-associated protein RdgC adopts a novel toroidal architecture for DNA binding"</p><p></p><p>Nucleic Acids Research 2007;35(8):2671-2681.</p><p>Published online 10 Apr 2007</p><p>PMCID:PMC1885664.</p><p>© 2007 The Author(s)</p> Ribbon diagrams and electrostatic potential at the molecular surface are shown for RdgC, gp45 of T4 DNA polymerase, human PCNA, DNA polymerase III β subunit and RecR. The molecular surface was colored according to the electrostatic potential (positive in blue and negative in red)

Recalibration and Validation of the Charlson Comorbidity Index in Korean Incident Hemodialysis Patients

<div><p>Background</p><p>Weights assigned to comorbidities to predict mortality may vary based on the type of index disease and advances in the management of comorbidities. We aimed to develop a modified Charlson comorbidity index (CCI) in incident hemodialysis patients (mCCI-IHD), thereby improving risk stratification for mortality.</p><p>Methods</p><p>Data on 24,738 Koreans who received their first hemodialysis treatment between 2005 and 2008 were obtained from the Korean Health Insurance dataset. The mCCI-IHD score were calculated by summing up the weights which were assigned to individual comorbidities according to their relative prognostic significance determined by multivariate Cox proportional hazards model. The modified index was validated in an independent nationwide prospective cohort (n=1,100).</p><p>Results</p><p>The Cox proportional hazards model revealed that all comorbidities in the CCI except ulcers significantly predicted mortality. Thus, the mCCI-IHD included 14 comorbidities with re-assigned severity weights. In the validation cohort, both the CCI and the mCCI-IHD were correlated with mortality. However, the mCCI-IHD showed modest but significant increases in <i>c</i> statistics compared with the CCI at 6 months and 1 year. The analyses using continuous net reclassification improvement revealed that the mCCI-IHD improved net mortality risk reclassification by 24.6% (95% CI, 2.5-46.7; <i>P</i>=0.03), 26.2% (95% CI, 1.0-51.4; <i>P</i>=0.04) and 42.8% (95% CI, 4.9-80.8; <i>P</i>=0.03) with respect to the CCI at 6 months and 1 and 2 years, respectively.</p><p>Conclusions</p><p>The mCCI-IHD facilitates better risk stratification for mortality in incident hemodialysis patients compared with the CCI, suggesting that it may be a preferred index for use in clinical practice and the statistical analysis of epidemiological studies.</p></div

Cumulative survival rate at each 1-year interval^*.

*<p>All data are presented as percent (%).</p><p>ITT, intention-to-treat; AT, as-treated; CCI, Charlson comorbidity index.</p

Comparision of hazard ratios of all independent predictors for mortality in the multivariate Cox analysis according to the age categories.

<p>Age, peripheral vascular disease, and hemiparesis were the factors by which mortality risk gradually increased with increasing age groups. However, the influences of Medical Aid, peritoneal dialysis, diabetes mellitus, congestive heart failure, liver disease, and any malignancy on the mortality sequentially decreased with aging. * Mortality rates between patients on hemodialysis and those on peritoneal dialysis were compared in the intention-to-treat analysis. HR, hazard ratio; CI, confidence interval.</p

Baseline characteristics.

*<p>Statistical differences according to age group were calculated in χ² test.</p><p>ITT, intention-to-treat; CCI, Charlson comorbidity index.</p

Kaplan-Meier survival curves and comparisons of survival rates by log-rank test.

<p>(A) Mortality rates gradually increased with the increment of age categories (<i>P = </i>0.0000). (B) Females showed better survival rate compared to males (<i>P = </i>0.0004). (C) Survival rate was better for patients without diabetes than that with diabetics (<i>P = </i>0.0000). (D) Patients covered by National Health Insurance experienced higher better survival rate compared to Medical Aid beneficiaries (<i>P = </i>0.0000). (E) Patients on hemodialysis experienced significant survival benefit over patients on peritoneal dialysis in the intention-to-treat analysis (<i>P = </i>0.0000). (F) As the modified Charlson comorbidity index for end-stage renal disease patients increased, survival rates significantly decreased (<i>P = </i>0.0000).</p

Weights for comorbidities in the development cohort.

<p>^aAdjusted for age, sex and all comorbidities</p><p>Weights for comorbidities in the development cohort.</p

Distribution of the CCI and mCCI-IHD scores for the development cohort.

<p>(A) Distribution of the CCI scores (n = 18,872), excluding patients with no comorbidity (n = 5,866). (B) Distribution of the mCCI-IHD scores (n = 18,087), excluding patients with no comorbidity (n = 6,651). The y-axis shows the number of subjects. The solid line represents a density curve, calculated by approximation, to identify the overall pattern and deviation. The vertical dotted lines (red) represents the 50^th and 90^th percentile values. CCI, Charlson comorbidity index; mCCI-IHD, modified Charlson comorbidity index for incident hemodialysis patients.</p

Results of the Cox proportional hazards analysis for all-cause mortality.

*<p>All-cause mortality was adjusted for all parameters with <0.10 of <i>P</i>-value in the univariate analysis.</p>†<p>Mortality rates between patients on hemodialysis and those on peritoneal dialysis were compared in the intention-to-treat analysis.</p><p>HR, hazard ratio; CI, confidence interval.</p

Survival curves obtained using the Kaplan-Meier method (A and B) and Cox regression analysis (C and D) in the validation cohort differentiated by the 4 risk groups of CCI (A and C) and mCCI-IHD (B and D).

<p>CCI, score 2 (n = 236, 21.5%); scores 3–4 (n = 537, 48.8%); scores 5–6 (n = 234, 21.3%); and score ≥7 (n = 93, 8.5%). mCCI-IHD, score 0 (n = 247, 22.5%); scores 1–4 (n = 480, 43.6%); scores 5–9 (n = 290, 26.4%); and score ≥10 (n = 83, 7.5%). ^aAdjusted for age, sex, health security system, timing of referral to nephrologist, primary cause of end-stage renal disease, body mass index, hemoglobin, albumin, calcium, and phosphorus. CCI, Charlson comorbidity index; mCCI-IHD, modified Charlson comorbidity index for incident hemodialysis patients.</p