Switch from bicarbonate hemodialysis to hemodiafiltration with online regeneration of the ultrafiltrate (HFR): effects on nutritional status, microinflammation, and beta-microglobulin

BACKGROUND: Hemodiafiltration (HFR) with on-line regeneration of the ultrafiltrate, a technique of hemodiafiltration in which the ultrafiltrate passes through a cartridge containing uncoated charcoal, has been shown to be safe, simple, and well tolerated and has been claimed to improve nutritional status or to prevent its deterioration while decreasing the inflammatory response via a reduced production of proinflammatory cytokines. The purpose of the present prospective study was to ascertain whether HRF improves the nutritional status, reduces microinflammation, and decreases serum beta2-microglobulin levels in patients with end-stage renal disease (ESRD). METHODS: Eight patients, four males and four females, with a mean age of 49.4 +/- 16.8 years, stable on hemodialysis over a period of 8.7 +/- 6.1 years and on standard 4-4.5 h three-times-a-week bicarbonate hemodialysis, were switched to three-times-a-week, 4-h HFR. At baseline and every two months for 12 months at mid-week, serum levels of urea, creatinine, albumin, total cholesterol, C-reactive protein, fibrinogen, complement, ferritin, beta2-microglobulin, intact parathyroid hormone (PTH), hemoglobin concentrations, and hematocrit and the EPO weekly dose were determined. At baseline and at the end of the study, the Malnutrition Inflammatory Score (MIS) was calculated. RESULTS: Nutritional and inflammatory parameters remained constant during the 12-month period of the study. After 12 months of HFR, the MIS trended to be lower, but the difference was not statistically significant. Serum beta2-microglobulin and PTH levels remained constant during all time intervals. Neither hematocrit nor hemoglobin changed over the course of the study as well as the weekly EPO dose. CONCLUSION: The change from bicarbonate hemodialysis to HFR was safe and well tolerated but was not associated with an improvement of nutritional and inflammatory parameters or a reduction of serum beta2-microglobulin levels.     

Staging systems in hepatocellular carcinoma

Staging systems are key to predict the prognosis of patients with cancer, to stratify the patients according to prognostic variables in the setting of clinical trials, to allow the exchange of information among researchers, and finally to guide the therapeutic approach. The current knowledge of the disease, however, prevents recommendation of a staging system that can be used world-wide. The conventional staging systems for hepatocellular carcinoma (HCC), such as the Okuda stage or the TNM stage have shown important limitations in classifying patients. Several new systems have been proposed recently, and only three of them have been validated at this point. The BCLC staging classification links the stage of the disease to a specific treatment strategy. The JIS score has been proposed and used in Japan, although it needs Western validation. The CLIP score is used in patients with advanced tumors. Several reasons explain the difficulty in identifying a world-wide system. First, HCC is a complex neoplasm inserted on a pre-neoplastic cirrhotic liver, and thus variables of both diseases leading to death should be taken into account. Second, the disease is very heterogeneous around the world, and this reflects different underlying epidemiological backgrounds and risk factors. Third, HCC is the sole cancer treated by transplantation in a small proportion of patients. Fourth, only around 20% of the cases are currently treated by surgery, thus precluding the wide use of pathology-based systems, such as TNM. Finally, the potential relevance of a molecular signature identified in terms of outcome prediction is unknown, and further research is needed to obtain this valuable biological information that may aid in classifying the patients.     

Assessing the risk of mortality in paediatric cancer patients admitted to the paediatric intensive care unit: a novel risk score?

Intensive front-line protocols have improved survival in children with malignancies; however, intensive multimodal therapy of paediatric malignancies can be associated with a significant risk of serious adverse events. Common risk scores (PRISM, PRISM III, APACHE-II) fail to predict mortality in these patients. A retrospective chart analysis of 32 paediatric cancer patients admitted to the Paediatric Intensive Care Unit (PICU) at the University Hospital of Saarland between January 2001 and December 2003 for life-threatening complications was performed. The aim of this study was to assess risk factors for short-term outcome (survival vs. non-survival when leaving the PICU) and to develop a risk score to estimate outcome in these patients. Overall survival was good (25 of 32 patients). Mortality rate was significantly related to leukaemia/lymphoma ( P =0.029), to the number of organ failures ( P <0.0001), neutropenia ( P =0.001), septic shock ( P =0.025), mechanical ventilation ( P =0.01) and inotropic support ( P =0.01). Employing multiple logistic regression, the strongest predictor for poor outcome was the number of organ failures ( P <0.05). A risk score (cut-off value: >3 points for non-survival) which included the following risk factors (non-solid tumour, number of organ failures ( n >2), neutropenia, septic shock, mechanical ventilation, and inotropic medication) yielded a sensitivity of 7/7 (95% CI: 4.56–7.00), a specificity of 23/25 (95% CI: 18.49–24.75), a positive predictive value of 23/23 (95% CI: 19.80–23.00), and a negative predictive value of 7/9 (95% CI: 3.60–8.74) for the time of admission to the PICU. Conclusion:Although our risk of mortality score is of prognostic value in assessing short-term outcome in these patients, prospective validation in a larger study cohort is mandatory. Furthermore, it must be emphasised that this risk score must not be used for decision-making in an individual patient.     

Pharmacodynamics of chloral hydrate in former preterm infants

The aim of this study was to document the pharmacodynamics of chloral hydrate in former preterm infants at term post-conception age. The degree of sedation (COMFORT), feeding behaviour and cardiorespiratory events (bradycardic events, apnoeas) before and after administration of chloral hydrate (oral, 30 mg/kg) were prospectively evaluated in former preterm infants during procedural sedation. Characteristics at birth, during neonatal stay and at inclusion were collected. Paired Wilcoxon and McNemar tests were used to study the impact of chloral hydrate. Characteristics of infants who displayed severe bradycardic events were compared to infants in whom no bradycardic events were recorded (Mann Whitney U, Fischers exact). A significant increase in sedation (decrease COMFORT scale) was observed up to 12 h after administration. There was a minor but significant decrease in oral intake (161 to 156 ml/kg/day, P <0.01). A significant increase in the number of bradycardic events (<80/min: 38 to 82 events, of which <70/min: 30 to 79 of which <60/min: 15 to 45; at least P <0.01) and in the duration of the most severe bradycardic event (8–12.5 s) was observed. Therefore, further inclusion was stopped when 26 neonates were included. Infants who displayed severe bradycardic (<60/min) events ( n =13) after administration of chloral hydrate had a lower gestational age at birth without difference in post-conception age at inclusion. Conclusion:Chloral hydrate was associated with an increase in unintended side-effects in former preterm infants, likely reflecting population specific pharmacodynamics and kinetics of chloral hydrate.     

Parkinsonism with excessive daytime sleepiness

Abstract Background Parkinsonian patients with excessive daytime sleepiness (EDS), hallucinations, REM sleep behavior disorder (RBD), short mean sleep latencies, and sleep-onset REM periods (SOREMP) on multiple sleep latency tests (MSLT) have been reported. In these patients a narcolepsy-like pathophysiology of sleep-wake disturbances has been suggested. Patients and methods We studied 14 consecutive patients with Parkinsonism and EDS. Standard studies included assessment of duration and severity of Parkinsonism (Hoehn & Yahr score), Epworth sleepiness score (ESS), history of REM-symptoms (RBD/hallucinations/sleep paralysis/cataplexy-like episodes), polysomnography (PSG),MSLT, and measurement of cerebrospinal fluid (CSF) levels of hypocretin-1 (orexin A). Results There were 12 men and 2 women (mean age 69 years; range 54–82). The mean duration and the Hoehn & Yahr score were 6.3 years and 2.2, respectively. Diagnoses included idiopathic Parkinsons disease (IPD, n=10), dementia with diffuse Lewy bodies (n=3), and multisystem atrophy (n=1). The ESS was 10 in all patients (mean 12; range 10–18). REM-symptoms were reported by all but two patients (hallucinations: n=9; RBD: n=9).None of the patients reported cataplexy-like symptoms or sleep paralysis. On PSG sleep apnea (apnea hypopnea index > 10/h, n=7), periodic limb movements during sleep (PLMS-index > 10/h, n=6), and features of RBD (n=5) were found. On MSLT mean sleep latency was < 5 minutes in 10 patients, and SOREMP were found in two patients. When compared with controls (n=20, mean 497 pg/ml; range 350–603), CSF hypocretin-1 levels were normal in 8 patients and low in 2 patients (221 and 307 pg/ml, respectively). Conclusion These findings do not support the hypothesis of a final common pathway in the pathophysiology of narcolepsy and Parkinsonism with EDS. Sleep apnea and PLMS may play a so-far underestimated role in the pathogenesis of EDS in Parkinsonian patients.     

Comparison of different screening tests for detecting diabetic foot neuropathy

INTRODUCTION: Regarding the major role of sensory neuropathy in diabetic foot ulcers, the use of an appropriate screening test for early detection of this neuropathy has a crucial role in the management of diabetic foot disorders. As there were no previous studies that performed all screening tests in the same group of patients, we performed all tests in a single group of diabetic patients and compared them to find out the possible differences between the results. METHODS: A total of 142 diabetic outpatients at Shariati Teaching Hospital were chosen by systematic randomized selection. Different screening tests for detecting neuropathy in diabetic foot such as symptom and sign scores, Michigan Neuropathy Disability Score (MNDS), and testing by a monofilament were performed for each patient. RESULTS: According to the neuropathy symptom score, 54.9% of the patients were neuropathic, their score was higher than 5, and by neuropathy sign score, 10.1% were neuropathic with a score higher than 6. Regarding MNDS, 42.7% of the subjects were neuropathic, with a score higher than 3. Finally, 23.9% were unable to sense at least one point in the monofilament examination. CONCLUSIONS: There were obvious differences between the results of different methods in our study. However, there were significant correlations between them, except between sign and symptom score methods. For determining the most reliable screening test, further studies are needed to compare these methods with a gold standard test and reveal the specificity and sensitivity of these tests.     

MELD Score as a Predictor of Early Death in Patients Undergoing Elective Transjugular Intrahepatic Portosystemic Shunt (TIPS) Procedures

Purpose To Evaluate the MELD score as a predictor of 30-day mortality in patients undergoing elective TIPS procedures.Methods This was a retrospective, IRB-approved study. The medical records of all patients who underwent a TIPS procedure between May 1, 1999 and June 1, 2003 in a single institution were reviewed. Patients who underwent elective TIPS were selected. Elective TIPS was performed in 119 patients with a mean age of 55.1 (± 9.6) years. The MELD and Child-Pugh scores before TIPS, etiology of cirrhosis, portosystemic gradients before and after TIPS, procedure time, and procedural complications were obtained from the medical records. The MELD and Child-Pugh scores before TIPS were compared between the survivor group (SG) and the early death (EDG) group. The early death rate was calculated for MELD score subgroups (1–10, 11–17, 18–24, and >24). Data were analyzed using the Fisher exact test, chi-square test and independent-sample t-test. A p value of less than 0.05 was considered significant.Results Technical success rate was 100%. The early death rate was 10.9% (13/119). The mean MELD scores before TIPS were 19.4 (± 5.9) (EDG) and 14 (± 4.2) (SG) (p=0.025). The early death rate was highest in the pre-TIPS MELD > 24 subgroup. The Child-Pugh scores were 9.0 (± 1.6) (SG) and 9.8±1.06 (EDG) (p=0.08). The mean portosystemic gradients before TIPS were 20.5 (± 7.7) mmHg (EDG) and 22.7 (± 7.3) (SG) (p > 1) and the mean portosystemic gradients after TIPS were 6.5 (± 3.5) (EDG) and 6.9 (± 2.4) (SG) (p > 1). The mean procedural times were 95.6 (± 8.4) min (EDG) and 89.2 (± 7.5) min (SG) (p > 1). No early death was attributed to a fatal complication during TIPS.Conclusion The MELD score is useful in identifying patients at a higher risk of early death after an elective TIPS. On th basis of our results, we do not endorse elective TIPS in patients with MELD scores > 24.     

Evaluation of general joint laxity, shoulder laxity and mobility in competitive swimmers during growth and in normal controls

The aim of the study was to evaluate differences between competitive swimmers and a reference group of school children concerning general joint laxity, laxity of the glenohumeral joint and range of motion in the shoulder. Materials and methods. Competitive swimmers (n = 120) were compared with references consisting of age and gender matched school children (n = 1277). General joint laxity was evaluated with the Beighton score. Anterior glenohumeral laxity was assessed according to the drawer test, and inferior glenohumeral laxity according to the sulcus test. Shoulder rotation was measured with a goniometer. RESULTS: Male swimmers of both age groups showed a higher degree of general joint laxity compared with the reference group while 9-year-old female swimmers alone had a lower degree of general joint laxity compared with references. No significant difference concerning shoulder laxity was noticed between groups. There was a decreased internal rotation in male and female swimmers as compared with the reference group. External rotation was reduced in female swimmers as compared with the female references. The same result was observed in male swimmers, but only at the age of 12 years. CLINICAL CONSEQUENCE: Competitive swimming in children seems to lead to a decreased range of motion with regard to shoulder rotation. However, the reason for this is still unclear and further investigations are needed.     

Growth hormone and body composition in children younger than 2 years with Prader-Willi syndrome

OBJECTIVES: To assess body composition of infants with Prader-Willi syndrome (PWS) by using deuterium dilution and investigating the efficacy of early institution of growth hormone (GH) therapy in increasing lean mass (LM) and preventing massive obesity. STUDY DESIGN: One group of 11 children with PWS <2 years before and during 30-month GH therapy (GH group) was compared with 6 infants administered only coenzyme Q(10) for 1 year (Q10 group). LM adjusted for height (LM(Ht)) and relative fat mass (%FM(Age)) standard deviation scores (SDS) were calculated from data of 95 healthy children. RESULTS: Initially, LM(Ht) of all patients was below the normal average. LM(Ht) decreased by -0.46 +/- 0.3 SD (P=.03) per year in the Q10 group but rose by 0.25 +/- 0.3 SD (P=.02) per year during GH therapy, normalizing after 30 months (-0.70 +/- 1.0 SD). Despite low to normal weight for height (WfH), %FM(Age) was above the normal average (GH group, 31.0% +/- 4.5%, Q10 group, 32.4% +/- 9.5%). In the Q10 infants, %FM(Age) increased by 0.71 +/- 0.7 SD per year, whereas in the GH group, %FM(Age) remained more stable up to 30 months. CONCLUSIONS: Diminished LM(Ht) found in infants with PWS further declines during the early years. Early institution of GH therapy lifts LM(Ht) into the normal range and delays fat tissue accumulation.