Plasma levels of vitamin E and carotenoids are decreased in patients with nonalcoholic steatohepatitis (NASH)

Objectives

Oxidative stress is suggested to play an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH). The present study was aimed to compare plasma levels of antioxidants in patients suffering from NASH and healthy controls.

Methods

Plasma levels of the antioxidants α-tocopherol, γ-tocopherol, lutein, zeaxanthin, β-cryptoxanthin, lycopene, α-carotene β-carotene were determined in 57 patients with biopsy-proven NASH and 40 healthy controls.

Results

Levels of α-tocopherol (22.4 vs. 26.8 nmol/ ml; p < 0.01), lutein (0.19 vs. 0.33 nmol/ml; p < 0.0001), zeaxanthin (0.04 vs. 0.08 nmol/ml; p < 0.0001), lycopene (0.15 vs. 0.42 nmol/ml; p < 0.0001), α-carotene (0.03 vs. 0.06 nmol/ml; p < 0.005) and β-carotene (0.25 vs. 0.39 nmol/ml; p < 0.01) were significantly decreased in NASH patients compared to controls. Age, aminotransferase status (ALT, AST) and BMI were not correlated with the levels of tocopherols or carotenoids.

Conclusions

Given the decreased levels supplementation of lipophilic antioxidants might be a rational treatment option for patients with NASH.     

Treatment during primary HIV infection does not lower viral set point but improves CD4 lymphocytes in an observational cohort

Objective

To investigate if early treatment of primary HIV-1 infection (PHI) reduces viral set point and/or increases CD4 lymphocytes.

Methods

Analysis of two prospective multi-centre PHI cohorts. HIV-1 RNA and CD4 lymphocytes in patients with transient treatment were compared to those in untreated patients. Time to CD4 lymphocyte decrease below 350/μl after treatment stop or seroconversion was calculated using Kaplan-Meier and Cox-PH-regression analyses.

Results

156 cases of PHI were included, of which 100 had received transient HAART (median treatment time 9.5 months) and 56 remained untreated. Median viral load (563000 cop/ml vs 240000 cop/ml; p < 0.001) and median CD4 lymphocyte (449/μl vs. 613/μl; p < 0.01) differed significantly between treated and untreated patients. Median viral load was 38056 copies/ml in treated patients (12 months after treatment stop) and 52880 copies/ml in untreated patients (12 months after seroconversion; ns). Median CD4 lymphocyte change was +60/μl vs. -86/μl (p = 0.01). Median time until CD4 lymphocytes decreased to < 350/μl (including all patients with CD4 lymphocytes < 500/μl during seroconversion) was 20.7 months in treated patients after treatment stop and 8.3 months in untreated patents after seroconversion (p < 0.01). Cox-PH analyses adjusting for baseline VL, CD4 lymphocytes, stage of early infection and symptoms confirmed these differences.

Conclusions

Treatment during PHI did not lower viral set point. However, patients treated during seroconversion had an increase in CD4 lymphocytes, whereas untreated patients experienced a decrease in CD4 lymphocytes. Time until reaching CD4 lymphocytes < 350/μl was significantly shorter in untreated than in treated patients including patients with CD4 lymphocytes < 500/μl during seroconversion.     

Effect of renal sympathetic nerve on adrenergically and angiotensin II-induced renal vasoconstriction in normal Wistar-Kyoto rats

Background

This study examined the effect of renal sympathetic innervation on adrenergically and angiotensin II (Ang II)-induced renal vasoconstriction in Wistar-Kyoto (WKY) rats.

Methods

Forty-eight WKY rats were treated with either losartan (10 mg/kg/day p.o.) or carvedilol (5 mg/kg/day p.o.) or a combination of them (10 mg/kg/day + 5 mg/kg/day p.o.) for 7 days. On day 8, the rats were anaesthetized, and renal vasoconstrictor experiments were carried out. A group of rats was subjected to acute unilateral renal denervation during the acute study. Changes in the renal vasoconstrictor responses were determined in terms of reductions in renal blood flow caused by Ang II, noradrenaline (NA), and methoxamine (ME).

Results

In normal animals, losartan decreased (P < 0.05) the renal vasoconstrictor response to Ang II but not to NA or ME. Carvedilol treatment, however, blunted (P < 0.05) the renal vasoconstrictor responses to Ang II and adrenergic agonists. Combination of losartan and carvedilol blunted (P < 0.05) the renal vasoconstrictor response to Ang II but augmented the responses to NA and ME (all P < 0.05). Interestingly, when denervated rats were treated with the same combination, there was a reduction (P < 0.05) in the renal vasoconstrictor responses to Ang II and adrenergic agonists.

Conclusions

Data suggest that the renal sympathetic nerve contributes to adrenergic agonist-mediated renal vasoconstrictions in normal rats. The data further indicate an interactive relationship between renin-angiotensin and sympathetic nervous systems in modulating adrenergically and Ang II-induced renal vasoconstriction in WKY rats.     

The role of surgery for pancreatic cancer: a 12-year review of patient outcome

Introduction

Pancreatic cancer has a poor prognosis with <5% alive at 5 years, despite active surgical treatment. The study aim was to review patients undergoing pancreatic resection and assess the effect of clinical and pathological parameters on survival.

Patients and methods

All patients who had undergone radical pancreatic surgery, January 1996 to December 2008, were identified from the unit database. Additional information was retrieved from the patient records. The demographic, clinical, and pathological records were recorded using Microsoft Excel. Survival was assessed using Kaplan-Meier and predictors of survival determined by multinominal logistic regression and log rank test.

Results

126 patients were identified from the database. The majority (106) had a Whipple''s procedure, 14 had a distal pancreatectomy and 6 had local periampullary excision. The average age of the Whipple''s group of patients was 61.7 years (± 11.7) with most procedures performed for malignancy (n=100). Survival was worse with adenocarcinoma compared to all other pathologies (p=0.013), while periampullary tumours had a better prognosis compared to other locations (p=0.019). Survival decreased with poorer differentiation (p=0.001), increasing pT (p<0.001) and pN stage (p<0.001). Survival was worse with perineural (p=0.04) or lymphovascular invasion (p=0.05). A microscopic postive resection margin (R1) was associated with a worse survival (p=0.007). Tumour differentiation (p=0.001) and positive nodal status (p<0.001) were found to be independent predictors of mortality.

Conclusion

Tumour differentiation and nodal status are important predictors of outcome. A positive resection margin is associated with a poorer survival.     

Full impact of laboratory information system requires direct use by clinical staff: cluster randomized controlled trial

Objective

To evaluate the time to communicate laboratory results to health centers (HCs) between the e-Chasqui web-based information system and the pre-existing paper-based system.

Methods

Cluster randomized controlled trial in 78 HCs in Peru. In the intervention group, 12 HCs had web access to results via e-Chasqui (point-of-care HCs) and forwarded results to 17 peripheral HCs. In the control group, 22 point-of-care HCs received paper results directly and forwarded them to 27 peripheral HCs. Baseline data were collected for 15 months. Post-randomization data were collected for at least 2 years. Comparisons were made between intervention and control groups, stratified by point-of-care versus peripheral HCs.

Results

For point-of-care HCs, the intervention group took less time to receive drug susceptibility tests (DSTs) (median 9 vs 16 days, p<0.001) and culture results (4 vs 8 days, p<0.001) and had a lower proportion of ‘late’ DSTs taking >60 days to arrive (p<0.001) than the control. For peripheral HCs, the intervention group had similar communication times for DST (median 22 vs 19 days, p=0.30) and culture (10 vs 9 days, p=0.10) results, as well as proportion of ‘late’ DSTs (p=0.57) compared with the control.

Conclusions

Only point-of-care HCs with direct access to the e-Chasqui information system had reduced communication times and fewer results with delays of >2 months. Peripheral HCs had no benefits from the system. This suggests that health establishments should have point-of-care access to reap the benefits of electronic laboratory reporting.     

Long term clinical outcome and bleeding complications among hospital survivors with acute coronary syndromes

Objective

To examine the 21 month clinical outcome and bleeding complications in hospital survivors with non‐ST segment elevation acute coronary syndromes (NSTEACS) who were discharged with combined clopidogrel and aspirin anti‐thrombotic therapy, and compare with those having ST segment elevation myocardial infarction (STEMI) who were discharged with aspirin alone.

Design

Observational study.

Setting

A large university hospital.

Patients

224 patients were admitted to hospital with either NSTEACS or STEMI, and survived to discharge between 1 October 2001 and 31 December 2002.

Main outcome measures

Cardiovascular death, total death, new myocardial infarction, unstable angina requiring hospitalisation, stroke or transient ischaemic attack, coronary revascularisation; and fatal, life threatening, major and minor bleeding over 21 months after discharge.

Results

Despite having no or small infarct (median maximum creatine kinase 155 v 1295 u/l; p<0.001) and taking more antianginal drugs, patients with NSTEACS had similar rates of cardiovascular death (9.5% v 8.3%; p = NS), new myocardial infarction (9.5% v 6.5%; p = NS) or unstable angina requiring hospitalisation (15.5% v 10.2%; p = NS) when compared with STEMI. Fatal, life threatening or major bleeding were <1% in both groups (p = NS); and minor bleeding occurred in 4.3% NSTEACS and 2.8% STEMI patients respectively (p = NS).

Conclusions

Patients with NSTEACS had a similar and unfavourable long term outcome when compared with STEMI. There was no difference in serious bleeding complications between both groups.     

Long term prognosis of heart failure after acute coronary syndromes without ST elevation

Background

Information about long term outcomes of patients with acute coronary syndromes (ACS) who have clinically diagnosed heart failure is scarce.

Methods

In a UK registry, this study evaluated patients with non‐ST elevation ACS, recording treatment, and clinical outcomes for six months. In a subgroup, a four year mortality follow up was performed to estimate the impact of the clinical diagnosis of heart failure on survival.

Results

Of 1046 patients, 139 (13%) had a history of clinically diagnosed heart failure. At discharge, ACE inhibitors were prescribed for 58% and 28%, of those with and without a history of heart failure respectively (p<0.001). Rates of angiography, percutaneous intervention, and coronary artery bypass graft were 17.3% and 29.2% (p = 0.003), 5.0% and 8.4% (p = 0.17), and 5.0% and 7.5% (p = 0.3) for these groups respectively. Death or new myocardial infarction at six months occurred in 22% and 10% (p<0.001) and at four years death occurred in 60% and 20% of these groups respectively (p<0.001). In a multivariate analysis prior heart failure carried an odds ratio of 2.0 (p = 0.001) for death or myocardial infarction at six months and 2.4 (p<0.001) for death over four years. New heart failure was associated with an increased risk of death at six months (20% compared with 5%, p<0.001).

Conclusion

A clinical history of heart failure carries a substantial risk of death in patients admitted with ACS without ST elevation. Nearly 60% of those with prior heart failure are dead after four years. After adjustment for confounding factors, prior heart failure more than doubles the risk compared with those with no history.     

Improved quality and efficiency after the introduction of physician-led team triage in an emergency department

Background

Overcrowding in the emergency department (ED) may negatively affect patient outcomes, so different triage models have been introduced to improve performance. Physician-led team triage obtains better results than other triage models. We compared efficiency and quality measures before and after reorganization of the triage model in the ED at our county hospital.

Materials and methods

We retrospectively compared two study periods with different triage models: nurse triage in 2008 (baseline) and physician-led team triage in 2012 (follow-up). Physician-led team triage was in use during day-time and early evenings on weekdays. Data were collected from electronic medical charts and the National Mortality Register.

Results

We included 20,073 attendances in 2008 and 23,765 in 2012. The time from registration to physician presentation decreased from 80 to 33 min (P < 0.001), and the length of stay decreased from 219 to 185 min (P < 0.001) from 2008 to 2012, respectively. All of the quality variables differed significantly between the two periods, with better results in 2012. The odds ratio for patients who left before being seen or before treatment was completed was 0.62 (95% confidence interval 0.54–0.72). The corresponding result for unscheduled returns was 0.36 (0.32–0.40), and for the mortality rates within 7 and 30 days 0.72 (0.59–0.88) and 0.84 (0.73–0.97), respectively. The admission rate was 37% at baseline and 32% at follow-up (P < 0.001).

Conclusion

Physician-led team triage improved the efficiency and quality in EDs.     

Safety and efficacy after switch to a saquinavir-containing antiretroviral regimen in protease inhibitor pretreated HIV-positive patients

Objective

The RAINBOW survey is a multinational observational study assessing the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r), using the 500 mg film-coated SQV formulation, in routine clinical practice. This analysis presents data from the German subgroup of protease inhibitor (PI)-pretreated, but SQV-naïve patients.

Methods

Multicenter, prospective, open-label, 48 week cohort study. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 48. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 48.

Results

A total of 426 patients were included in the analysis. The proportion of patients with HIV RNA levels < 50 copies/mL at week 48 was 60.3% (compared with 31.7% at switch to SQV/r) (intent-to-treat, last observation carried forward analysis). After 48 weeks, median CD4 count increased by +61 cells/mm³ from baseline (p < 0.01) and 60.3% of patients achieved HIV-1 RNA < 50 copies/mL. Median changes in fasting triglyceride levels (stratified according to baseline level) at week 48 were: +14 mg/dL (IQR -8; 57) for patients with baseline triglyceride < 200 mg/dL; -50 mg/dL (IQR -139; 0) for baseline triglyceride 200-750 mg/dL, and -656 mg/dL (IQR 1024; 0) for baseline triglyceride > 750 mg/dL (p < 0.01 for all). Median changes in fasting total cholesterol (TC) levels (stratified according to baseline) were +16 mg/dL (IQR -3; 43) for patients with baseline TC < 200 mg/dL (p < 0.01), -3 mg/dL (IQR -25; 25) for baseline TC 200-300 mg/dL (p = 0.4), and -47 mg/dL (IQR -87; -4) for baseline TC > 300 mg/dL (p < 0.01). No significant changes in liver enzymes or bilirubin were observed. SQV treatment was discontinued in 22% of patients, 6% due to side effects.

Conclusions

These data confirm the efficacy and tolerability of SQV/r in PI-experienced, SQV-naïve patients treated in a real-life clinical setting. Of particular relevance are the improvements in triglycerides and TC levels observed in patients with baseline grade III-IV elevations.     

Ethnic differences in control of cardiovascular risk factors in patients with type 2 diabetes attending an Inner London diabetes clinic

Background

South Asians have higher risk of diabetic complications compared with white Europeans. The aim of this study was to compare management of cardiovascular risk factors between Bangladeshis and white Europeans.

Methods

A retrospective survey of all diabetic patients attending an Inner London hospital diabetic clinic over one year was undertaken. Data were obtained from the hospital diabetes database: presence of macrovascular (myocardial infarction, angina, stroke, transient ischaemic attack, cardiac intervention) and microvascular disease (neuropathy, retinopathy, and nephropathy), glycated haemoglobin, blood pressure, lipids, smoking, and body mass index (BMI) were all determined.

Results

A total of 1162 white European and 912 Bangladeshi patients with full data available were included in the analyses. The groups were equivalent in age, sex, duration of diabetes. Compared with white Europeans, Bangladeshis had more macrovascular disease (19.5% v 11.9% p<0.01), sight threatening retinopathy (7.2% v 3.8%, p<0.01), and nephropathy (15.3% v 9.1%, p<0.01). In addition, Bangladeshis had significantly more male smokers (28.1% v 22.1%, p<0.01), poorer glycaemic control (mean HbA1c 8.6% v 8.1%, p = 0.039), greater proportion with uncontrolled hypercholesterolaemia (total cholesterol >5.0 mmol/l, 31.6% v 26% p = 0.05), and poorer control of blood pressure (proportion with BP >140/80 mm Hg, 43.2% v 32.1%, p<0.01).

Conclusions

South Asians with type 2 diabetes have poorer glycaemic, blood pressure, and lipid control than white Europeans. The reasons for this are probably multifactorial.     

Short-term outcome after posterior versus lateral surgical approach for total hip arthroplasty - a randomized clinical trial*

Purpose

Currently, total hip replacement (THR) is most commonly performed via a posterior or a direct lateral approach, but the impact of the latter on the invention''s outcome has yet not been quantified.

Methods

We compared the short-term outcome of cementless THR using the both approaches in a prospective, randomized controlled trial. 60 patients with unilateral osteoarthritis were included. Outcome assessment was performed one day before surgery and one week, four weeks, six weeks and 12 weeks after surgery, respectively, using the Harris Hip score as primary objective.

Results

We found no significant difference in the intraindividual Harris Hip Score improvement at the pre-and three months post-operative assessments between both treatment groups (p = 0.115). However, Harris Hip scores and most functional and psychometric secondary endpoints showed a consistent tendency of a slightly better three months result in patients implanted via the posterior approach. In contrast a significant shorter operating time of the direct lateral approach was recorded (67 minutes versus 76 minutes, p < 0.001).

Conclusion

In our opinion this slightly better short-term functional outcome after posterior approach is not clinical relevant. However, to make definitive conclusions all clinical relevant factors (i.e. mid- to long-term function, satisfaction, complication rates and long-term survival) have to be taken into account. Level of evidence: I - therapeutic     

Significance of decoy receptor 3 in sera of hepatocellular carcinoma patients

Objective

Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor superfamily, is amplified and over-expressed in various cancers. The objective of the present study was to investigate the concentration of DcR3 in sera of hepatocellular carcinoma (HCC) patients and its clinical significance.

Methods

Serum concentrations of DcR3 were measured by enzyme-linked immunosorbent assay (ELISA) in 67 patients with HCC, 8 with liver cirrhosis, 17 with cholecystitis, and in 28 healthy individuals. Immunohistochemistry was employed to access protein expression of DcR3 in the corresponding HCC tissues.

Results

Serum concentrations of DcR3 in patients with HCC or cirrhosis were significantly higher than in healthy individuals (P < 0.01). Moreover, serum concentrations of DcR3 in HCC patients were associated with TNM stage, para-cirrhosis, capsular infiltration, and metastasis or recurrence of disease (P < 0.05). There was a positive correlation between the serum concentration of DcR3 and protein expression in HCC tissues (r = 0.472, P < 0.01).

Conclusions

The high serum concentration of DcR3 might play a certain role in pathogenesis, progress, and metastasis of HCC. Moreover, DcR3 might serve as a valuable molecular indicator in early diagnosis and contribute to predicting the clinical outcome in HCC patients.     

Effect of an acute medical admission unit on key quality indicators assessed by funnel plots

Objective

To determine the effect of the introduction of an acute medical admissions unit (AMAU) on key quality efficiency and outcome indicator comparisons between medical teams as assessed by funnel plots.

Methods

A retrospective analysis was performed of data relating to emergency medical patients admitted to St James'' Hospital, Dublin between 1 January 2002 and 31 December 2004, using data on discharges from hospital recorded in the hospital in‐patient enquiry system. The base year was 2002 during which patients were admitted to a variety of wards under the care of a named consultant physician. In 2003, two centrally located wards were reconfigured to function as an AMAU, and all emergency patients were admitted directly to this unit. The quality indicators examined between teams were length of stay (LOS) <30 days, LOS >30 days, and readmission rates.

Results

The impact of the AMAU reduced overall hospital LOS from 7 days in 2002 to 5 days in 2003/04 (p<0.0001). There was no change in readmission rates between teams over the 3 year period, with all teams displaying expected variability within control (95%) limits. Overall, the performance in LOS, both short term and long term, was significantly improved (p<0.0001), and was less varied between medical teams between 2002 and 2003/04.

Conclusions

Introduction of the AMAU improved performance among medical teams in LOS, both short term and long term, with no change in readmissions. Funnel plots are a powerful graphical technique for presenting quality performance indicator variation between teams over time.     

CpG island methylation of TMS1/ASC and CASP8 genes in cervical cancer

Background

Gene silencing associated with aberrant methylation of promoter region CpG islands is an acquired epigenetic alteration that serves as an alternative to genetic defects in the inactivation of tumor suppressor and other genes in human cancers.

Aims

This study describes the methylation status of TMS1/ASC and CASP8 genes in cervical cancer. We also examined the prevalence of TMS1/ASC and CASP8 genes methylation in cervical cancer tissue and none - neo plastic samples in an effort to correlate with smoking habit and clinicopathological features.

Method

Target DNA was modified by sodium bisulfite, converting all unmethylated, but not methylated, cytosines to uracil, and subsequently amplified by Methylation Specific (MS) PCR with primers specific for methylated versus unmethylated DNA. The PCR product was detected by gel electrophoresis and combined with the clinical records of patients.

Results

The methylation pattern of the TMS1/ASC and CASP8 genes in specimens of cervical cancer and adjacent normal tissues were detected [5/80 (6.2%), 3/80 (3.75%)-2/80 (2.5%), 1/80 (1.2%) respectively]. No statistical differences were seen in the extent of differentiation, invasion, pathological type and smoking habit between the methylated and unmethylated tissues (P > 0.05).

Conclusion

The present study conclude that the frequency of TMS1/ASC and CASP8 genes methylation in cervical cancer are rare (< 6%), and have no any critical role in development of cervical cancer.     

A limited sampling strategy for estimation of the area under the curve (0 to 8 hours) of mycophenolic acid administered three times daily to liver transplant recipients

Objectives

Gastrointestinal side-effects caused by mycophenolic acid (MPA) are frequent in liver transplant recipients, and in these cases a switch from two to three daily doses is usually recommended. However, a limited sampling strategy for the estimation of MPA area under the curve from 0 to 8 hours (AUC_(0–8h)) has not been made.

Design and methods

In 22 liver transplant patients who were administered MPA three times daily, the trapezoidal extrapolated MPA AUC_(0–8h) values using a sampling time from 0 to 2 hours were calculated.

Results

A tentative therapeutic range for MPA AUC_(0–8h) of about 20–40 μg.h/mL is proposed, and in the 13 patients with supratherapeutic values the total leukocyte blood count was significantly lower than in the 9 patients with AUC_(0–8h) ≤ 40 μg.h/mL (P < 0.001). Significant negative correlations were found between the total leukocyte blood count and the MPA trough levels (r = −0.458; P < 0.05), AUC_(0–8h) (r = −0.479; P < 0.05), and AUC_(0–2h) (r = −0.437; P < 0.05). A significant correlation was found between the trapezoidal extrapolated AUC_(0–8h) and trapezoidal AUC_(0–2h) results (r = 0.850; P < 0.001).

Conclusions

The trapezoidal extrapolated AUC_(0–8h), and possibly trapezoidal AUC_(0–2h), may be useful for routine therapeutic MPA monitoring in liver transplant recipients in which the dosing frequency is increased from twice to three times a day.     

Protein-network modeling of prostate cancer gene signatures reveals essential pathways in disease recurrence

Objective

Uncovering the dominant molecular deregulation among the multitude of pathways implicated in aggressive prostate cancer is essential to intelligently developing targeted therapies. Paradoxically, published prostate cancer gene expression signatures of poor prognosis share little overlap and thus do not reveal shared mechanisms. The authors hypothesize that, by analyzing gene signatures with quantitative models of protein–protein interactions, key pathways will be elucidated and shown to be shared.

Design

The authors statistically prioritized common interactors between established cancer genes and genes from each prostate cancer signature of poor prognosis independently via a previously validated single protein analysis of network (SPAN) methodology. Additionally, they computationally identified pathways among the aggregated interactors across signatures and validated them using a similarity metric and patient survival.

Measurement

Using an information-theoretic metric, the authors assessed the mechanistic similarity of the interactor signature. Its prognostic ability was assessed in an independent cohort of 198 patients with high-Gleason prostate cancer using Kaplan–Meier analysis.

Results

Of the 13 prostate cancer signatures that were evaluated, eight interacted significantly with established cancer genes (false discovery rate <5%) and generated a 42-gene interactor signature that showed the highest mechanistic similarity (p<0.0001). Via parameter-free unsupervised classification, the interactor signature dichotomized the independent prostate cancer cohort with a significant survival difference (p=0.009). Interpretation of the network not only recapitulated phosphatidylinositol-3 kinase/NF-κB signaling, but also highlighted less well established relevant pathways such as the Janus kinase 2 cascade.

Conclusions

SPAN methodolgy provides a robust means of abstracting disparate prostate cancer gene expression signatures into clinically useful, prioritized pathways as well as useful mechanistic pathways.     

Liver volume measurement: reason of the difference between in vivo CT-volumetry and intraoperative ex vivo determination and how to cope it

Purpose

Volumetric assessment of the liver regularly yields discrepant results between pre- and intraoperatively determined volumes. Nevertheless, the main factor responsible for this discrepancy remains still unclear. The aim of this study was to systematically determine the difference between in vivo CT-volumetry and ex vivo volumetry in a pig animal model.

Material and Methods

Eleven pigs were studied. Liver density assessment, CT-volumetry and water displacement volumetry was performed after surgical removal of the complete liver. Known possible errors of volume determination like resection or segmentation borders were eliminated in this model. Regression analysis was performed and differences between CT-volumetry and water displacement determined.

Results

Median liver density was 1.07 g/ml. Regression analysis showed a high correlation of r² = 0.985 between CT-volumetry and water displacement. CTvolumetry was found to be 13% higher than water displacement volumetry (p < 0.0001).

Conclusion

In this study the only relevant factor leading to the difference between in vivo CT-volumetry and ex vivo water displacement volumetry seems to be blood perfusion of the liver. The systematic difference of 13 percent has to be taken in account when dealing with those measures.     

The rainbow cohort: 96 week follow-up of saquinavir-containing regimens in previously antiretroviral therapy (ART)-naïve and pre-treated but protease inhibitor (PI)- naïve hiv-infected patients

Objective

We have previously reported data from the German cohort of the multinational observational prospective RAINBOW survey which assessed the tolerability and efficacy of ritonavir-boosted saquinavir (SQV/r)-containing regimens over 48 weeks in routine clinical practice. This analysis presents data from antiretroviral (ART)-naïve and pretreated but protease inhibitor (PI)-naïve patients treated in a long-term one line (96 weeks) follow-up of the initial study.

Methods

All ART-and PI-naïve patients from the initial RAINBOW cohort who had recorded data to one line 96 weeks of treatment were eligible for inclusion in the current analysis. Efficacy assessments included the proportion of patients with HIV-1 RNA < 50 and < 400 copies/mL and changes in CD4 cell count from baseline to week 96. Tolerability assessments included changes in liver enzymes and lipid levels from baseline to week 96. For evaluation of efficacy, intent-to-treat analysis, in which missing values were recorded as failure (ITT), and last-observation-carried-forward (LOCF) analysis were used. Metabolic parameters were assessed using LOCF analysis.

Results

The analysis included 175 ART-naïve and 109 pretreated but PI-naïve patients. After 96 weeks, a similar proportion of patients in the ART-naïve and in the pretreated but Pi-naïve group had HIV-1 RNA levels < 400 copies/mL (68.0% and 70.6% [ITT], respectively; 96.6% and 90.8% [LOCF], respectively). The proportion of patients with HIV RNA < 50 copies/mL was higher in the ART-naïve group compared with the pretreated but PI-naïve group (61.1% and 56.9% [ITT], respectively; 84.0% and 75.2% [LOCF], respectively). Median change in CD4 cell count from baseline to week 96 was''+263 cells/mm³ (IQR 170; 384. LOCF; p < 0.0001) in the ART-naïve group, and one line +181 cells/mm³ (IQR 60; 309. LOCF; p < 0.0001) in the pretreated but PI-naïve group. Treatment was well tolerated, with only 2.5% of patients withdrawing from treatment due to side effects. There were no clinically relevant changes in liver enzyme levels. Overall total cholesterol, triglyceride, and low-and high-density lipoprotein levels increased to week 96, although levels remained within normal ranges in the majority of ART-naïve and pretreated patients.

Conclusions

This follow-up analysis confirms the long term efficacy and tolerability of SQV/r in ART-naïve and pretreated but PI-naïve patients in the real-life clinical setting.     

Investigation and management of severe hyponatraemia in a hospital setting

Aims

To evaluate the assessment and management of severe hyponatraemia in a large teaching hospital.

Methods

Inpatients with serum sodium <125 mmol/l were identified prospectively from a laboratory database over a six month period. Notes were examined and data extracted. Case notes were carefully reviewed retrospectively by a consultant endocrinologist with regard to accuracy of the diagnosis and the appropriateness of investigations and management.

Results

104 patients with a serum sodium <125 mmol/l were identified. Mean (SD) age was 69 (14), 52% were female, mean hospital stay was 16 (12) days, and overall mortality 27%. Adequate investigations were rarely performed. Only 28 (26%) had plasma osmolality measured, 29 (27%) urine osmolality, 11 (10%) urinary sodium, 8 (8%) plasma cortisol, and 2 (2%) a short Synacthen test. Comparing the “ward” and “specialist review” diagnoses, there were significant discrepancies for “no cause found” (49% v 27%, p<0.001), alcohol (6% v 11% p<0.01), and syndrome of inappropriate antidiuresis (20% v 32%, p = 0.001). Treatment was often illogical with significant management errors in 33%. These included fluid restriction and intravenous saline given together (4%) and fluid restriction in diuretic induced hyponatraemia (6%). Mortality was higher in the group with management errors (41% v 20% p = 0.002).

Conclusion

Severe hyponatraemia is a serious condition, but its investigation and evaluation is often inadequate. Some treatment patterns seem to be arbitrary and illogical, and are associated with higher mortality.     

Impact of iron supplementation on schistosomiasis control in Zambian school children in a highly endemic area

Aim

To study impact of once weekly iron supplementation on praziquantel cure rate, Schistosoma haematobium reinfection, and haematological parameters in pupils aged between 9 and 15 years of age in Nchelenge district, Zambia.

Methods

Pupils in the intervention group received once weekly dose of ferrous sulphate at 200mg while those in the control received once weekly vitamin C at 100mg for up to 9 months. Both study groups received a single dose of praziquantel at baseline.

Results

S haematobium reinfection intensity was significantly lower in boys in the intervention group than in boys in the control group at 6 months (P<0.001) and 9 months (P<0.001) of supplementation. Significantly lower S haematobium reinfection intensity was found in girls in the intervention group than in girls in the control group only at 6 months of supplementation (P=0.018). Boys in the intervention group were 42% (Adjusted Risk Ratio =0.58, 95% confidence interval 0.39, 0.86) less likely to be reinfected with S haematobium than in the control group at 6 months follow up.

Conclusion

Once weekly iron supplementation can decrease S haematobium reinfection after 6 months and should be incorporated into school based schistosomiasis control programs in highly endemic areas.

Clinical trials.gov identifier

{"type":"clinical-trial","attrs":{"text":"NCT 00276224","term_id":"NCT00276224"}}NCT 00276224, sponsored by DBL-Institute for Health Research and Development, Denmark.