Chun-Soo Lim

High-Dose Versus Conventional-Dose Continuous Venovenous Hemodiafiltration and Patient and Kidney Survival and Cytokine Removal in Sepsis-Associated Acute Kidney Injury: A Randomized Controlled Trial

BACKGROUND Soluble inflammatory mediators are known to exacerbate sepsis-induced acute kidney injury (AKI). Continuous renal replacement therapy (CRRT) has been suggested to play a part in immunomodulation by cytokine removal. However, the effect of continuous venovenous hemodiafiltration (CVVHDF) dose on inflammatory cytokine removal and its influence on patient outcomes are not yet clear. STUDY DESIGN Prospective, randomized, controlled, open-label trial. SETTING & PARTICIPANTS Septic patients with AKI receiving CVVHDF for AKI. INTERVENTION Conventional (40mL/kg/h) and high (80mL/kg/h) doses of CVVHDF for the duration of CRRT. OUTCOMES Patient and kidney survival at 28 and 90 days, circulating cytokine levels. RESULTS 212 patients were randomly assigned into 2 groups. Mean age was 62.1 years, and 138 (65.1%) were men. Mean intervention durations were 5.4 and 6.2 days for the conventional- and high-dose groups, respectively. There were no differences in 28-day mortality (HR, 1.02; 95% CI, 0.73-1.43; P=0.9) or 28-day kidney survival (HR, 0.96; 95% CI, 0.48-1.93; P=0.9) between groups. High-dose CVVHDF, but not the conventional dose, significantly reduced interleukin 6 (IL-6), IL-8, IL-1b, and IL-10 levels. There were no differences in the development of electrolyte disturbances between the conventional- and high-dose groups. LIMITATIONS Small sample size. Only the predilution CVVHDF method was used and initiation criteria were not controlled. CONCLUSIONS High CVVHDF dose did not improve patient outcomes despite its significant influence on inflammatory cytokine removal. CRRT-induced immunomodulation may not be sufficient to influence clinical end points.

Prenatal growth pattern of the human maxilla.

Regarding maxillofacial morphogenesis there has been a long debate on the growth of the maxillary structure. Using 120 normal fetal maxillae of gestational ages from 16 to 41 weeks, palatal radiograms and frontal histologic sections were made. We have observed two pairs of accentuated growth areas in the fetal maxillae and named them primary growth centers to formulate the maxillary trapezoid (MT) by radiologic image. The MT is formed by four primary growth centers that are best demonstrated by palatal radiograms of the fetal maxilla as well as by frontal histologic sections. The dimensional increase in the MT during the fetal period is documented and statistically analyzed. From this series of results, we have suggested that the growth centers which demarcate the MT are the basic structures of the developing human maxilla. It was also found that the four primary growth centers are the most active sites for maxilla formation until 20 weeks of gestation and thereafter the growth of the maxilla is enhanced by the participation of the intramembranous bone formation along the periphery. This was in contrast to the central primary growth centers that have already finished maturation in the early fetal period and remain only as a peripherally radiating arrangement of thick trabecular bones.

Recalibration and validation of the Charlson comorbidity index in Korean incident hemodialysis patients.

Background 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. Methods 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). Results 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 c 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; P=0.03), 26.2% (95% CI, 1.0-51.4; P=0.04) and 42.8% (95% CI, 4.9-80.8; P=0.03) with respect to the CCI at 6 months and 1 and 2 years, respectively. Conclusions 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.

Immunohistochemical distribution of MAM-3 and MAM-6 antigens in developing salivary glands of the human fetus

SummaryThe immunohistochemical expression of MAM-3 and MAM-6 antigens was studied in developing human fetal salivary gland removed at autopsy of 22 normal fetuses of varying maturity (10–40 weeks of gestation). The onset of functional maturation in the fetal gland was seen at 21 weeks of gestational maturity. The acini and ducts then underwent distinct alterations in antigen expression with growth and maturation until the late developmental stage (33–40 weeks of gestation) when they resemble the adult salivary gland. The role of maturing duct cells in histogenesis of salivary gland tumours is discussed.

DEVELOPMENT AND VALIDATION OF THE MODIFIED CHARLSON COMORBIDITY INDEX IN INCIDENT PERITONEAL DIALYSIS PATIENTS: A NATIONAL POPULATION-BASED APPROACH

♦ Background: The utility of applying the Charlson comorbidity index (CCI) to peritoneal dialysis (PD) patients is disputed because the relative weight of each comorbidity in PD patients may be different from those in other chronic diseases. We aimed to develop and validate a modified CCI in incident PD patients (mCCI-IPD) for better risk stratification and prediction of mortality. ♦ Methods: The mCCI-IPD was developed using data from all Korean adult incident PD patients between 2005 and 2008 (n = 7,606). Multivariate Cox regression was used to determine new weights for the individual comorbidities in the CCI. The prognostic performance of the mCCI-IPD was validated in an independent cohort (n = 664) through c-statistics and continuous net reclassification improvement (cNRI). ♦ Results: A total of 75.5% of the patients in the development cohort had 1 or more comorbidities. The Cox proportional hazards model provided reassigned severity weights for the 11 comorbidities that significantly predicted mortality. In the validation cohort, the CCI and mCCI-IPD scores were both correlated with survival and showed no differences in their c-statistics. However, multivariate analyses using cNRI revealed that the mCCI-IPD provided a 38.2% improvement in mortality risk assessment compared with the CCI (95% confidence interval [CI], 15.3 – 61.0; p < 0.001). These significant reclassification improvements were observed consistently in subjects with events (cNRIEvent, 28.2% [95% CI, 6.9 – 49.5; p = 0.009]) and without events (cNRINon-event, 10.0% [95% CI, 1.7 – 18.2; p = 0.019]). ♦ Conclusions: Compared with the CCI, the mCCI-IPD showed better performance in mortality prediction for incident PD patients. Therefore, this tool may be used as a preferred index for statistical analysis and clinical decision-making.