004Topical Zinc Oxide for Open Pilonidal Wounds

Extended healing time and lack of documented effective treatments of sacrococcygeal pilonidal disease create substantial problems. Locally applied zinc oxide has been reported to promote wound healing. We have compared topical zinc oxide (3%) with placebo meshes for pilonidal wounds healing by secondary intention in a randomized, double‐blind, placebo‐controlled multicenter trial. Sixty‐four consecutive patients, 53 males, aged between 18 and 60 years (median 26 years) with excised pilonidal wounds were centrally randomized to local zinc oxide (30 mg/g, n = 33) or to placebo (n = 31) mesh treatment. Patients were followed with strict recording of beneficial and harmful effects. The median healing times were 54 days (42–71 days, interquartile range, n = 33) for the zinc group and 62 days (55–82 days, n = 31) for the placebo group. This difference was not statistically different (p = 0.32). Based on Cox regression analysis initial wound volume influenced healing negatively (p = 0.016) while smoking (p = 0.011) was associated with faster wound healing. Significantly (p < 0.01) more placebo (n = 12) than zinc oxide‐treated patients (n = 3) needed antibiotics postoperatively. Although topical zinc oxide increased (p < 0.001) wound fluid zinc levels (1830 ± 405 μM, mean ± SEM) compared with placebo (3.1 ± 1.6 μM) serum‐zinc levels did not differ significantly between the zinc (13.5 ± 0.4 μM) and placebo (12.8 ± 0.4 μm) groups on postoperative day 7. No adverse events were recorded. Topical zinc oxide treatment did not accelerate time to closure of open pilonidal wounds but was associated with reduced antibiotic usage.     

Serum testosterone concentrations in men with alcoholic cirrhosis: background for variation

Median serum testosterone concentration of men with alcoholic cirrhosis (n = 216) did not differ significantly from normal controls (n = 51), but serum testosterone concentrations varied by a factor 43.9 in patients compared to 3.2 in controls (P less than .001). Nineteen percent of the patients had serum testosterone concentrations above 30 nmol/L. Serum concentrations of sex-hormone-binding globulin (SHBG) were significantly (P less than .001) raised, and serum concentrations of calculated nonprotein-bound and non-SHBG-bound testosterone were significantly (P less than .001) decreased in patients compared to normal control values. A number of background variables were analyzed with reference to serum testosterone concentrations by means of multiple regression techniques after having divided the patients into groups (A, B, C) with decreasing liver function by a modification of the Child-Turcotte's criteria. The only significant (P less than .01) background variables associated with log serum testosterone concentrations were: group C (beta = -0.828), group B (beta = -0.222), age (years) (beta = -0.012), duration of hospitalization (days) (beta = -0.0077), and concentration of SHBG (nmol/L) (beta = 0.0044). Neither previous nor recent (within last six months) alcohol consumption influenced serum testosterone concentrations significantly, but about 50% of the patients had abstained from ethanol for two months or more. The same background variables as above were included as significantly (P less than .01) associated with log serum concentrations of calculated nonprotein-bound testosterone and calculated non SHBG-bound testosterone, except that SHBG was insignificantly associated to any of the two proportions and that testicular volume was significantly (P less than .05) associated with log non-SHBG bound testosterone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Liver pathology associated with the use of anabolic-androgenic steroids

Abstract: This review examines the liver-damaging side effects of anabolic-androgenic steroids (AAS). It seems that AAS can cause development of peliosis hepatis, subcellular changes of hepatocytes, hepatocellular hyperplasia and hepatocellular adenomas. On the other hand, it has not been convincingly proved that AAS can cause development of hepatocellular carcinomas when used in the usual therapeutic doses. Tumours reported as hepatocellular carcinomas caused by AAS seem to be hyperplastic lesions of a benign nature able to regress with withdrawal of the putative agent. The effects of untraditional combinations and high-dose AAS are not yet known, leaving the possibility of a carcinogenic effect in those cases.     

Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review

Context  Artificial and bioartificial support systems may provide a "bridge" for patients with severe liver disease to recovery or transplantation. Objective  To evaluate the effect of artificial and bioartificial support systems for acute and acute-on-chronic liver failure. Data Sources  Randomized trials on any support system vs standard medical therapy were included irrespective of publication status or language. Nonrandomized studies were included in explorative analyses. Trials were identified through electronic searches (Cochrane Hepato-Biliary Group Controlled Trials Register, Cochrane Library, MEDLINE, EMBASE, and the Chinese Medical Database), bibliographies, and contact with experts. Searches were conducted of the entire databases through September 2002. Study Selection  Of 528 references identified, 12 randomized trials with 483 patients were included. Eight nonrandomized studies were included in explorative analyses. Data Extraction  Data were extracted and trial quality was assessed independently by 3 reviewers (L.L.K., J.L., B.A-N.). The primary outcome measure was all-cause mortality. Results were combined on the risk ratio (RR) scale. Random-effects models were used. Sources of heterogeneity were explored through meta-regression and stratified meta-analyses. Data Synthesis  Of the 12 trials included, 10 assessed artificial systems for acute or acute-on-chronic liver failure and 2 assessed bioartificial systems for acute liver failure. Overall, support systems had no significant effect on mortality compared with standard medical therapy (RR, 0.86; 95% confidence interval [CI], 0.65-1.12). Meta-regression indicated that the effect of support systems depended on the type of liver failure (P = .03). In stratified meta-analyses, support systems appeared to reduce mortality by 33% in acute-on-chronic liver failure (RR, 0.67; 95% CI, 0.51-0.90), but not in acute liver failure (RR, 0.95; 95% CI, 0.71-1.29). Compared with randomized trials, nonrandomized studies produced significantly larger estimates of intervention effects (P = .01). Conclusion  This review suggests that artificial support systems reduce mortality in acute-on-chronic liver failure compared with standard medical therapy. Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure.      

The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial: rationale and design of a multicenter, randomized, placebo-controlled, clinical trial of metoprolol for patients with diabetes mellitus who are undergoing major noncardiac surgery

Background

Recent trials suggest that perioperative β-blockade reduces the risk of cardiac events in patients with a risk of myocardial ischemia who are undergoing noncardiac surgery. Patients with diabetes mellitus are at a high-risk for postoperative cardiac morbidity and mortality. They may, therefore, benefit from perioperative β-blockade.

Methods

The Diabetic Postoperative Mortality and Morbidity (DIPOM) trial is an investigator-initiated and -controlled, centrally randomized, double-blind, placebo-controlled, multicenter trial. We compared the effect of metoprolol with placebo on mortality and cardiovascular morbidity rates in patients with diabetes mellitus who were β-blocker naive, ≥40 years old, and undergoing noncardiac surgery. The study drug was given during hospitalization for a maximum of 7 days beginning the evening before surgery. The primary outcome measure is the composite of all-cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure leading to hospitalization or discovered or aggravated during hospitalization. Follow-up involves re-examination of patients at 6 months and collection of mortality and morbidity data via linkage to public databases. The study was powered on the basis of an estimated 30% 1-year event rate in the placebo arm and a 33% relative risk reduction in the metoprolol arm. The median follow-up period was 18 months.

Results

Enrollment started in July 2000 and ended in June 2002. A total of 921 patients were randomized, and 54% of these patients had known cardiac disease, hypertension, or both.

Conclusion

The results of this study may have implications for reduction of perioperative and postoperative risk in patients with diabetes mellitus who are undergoing major noncardiac surgery.     

Meta‐analysis of propylthiouracil for alcoholic liver disease – a Cochrane Hepato‐Biliary Group Review

Abstract: Aims/Background: The aim of this review was to determine the benefits and adverse effects of propylthiouracil for patients with alcoholic liver disease. Methods: Systematic Cochrane Review of randomised clinical trials. The Cochrane Hepato‐Biliary Controlled Clinical Trials Register, The Cochrane Library, MEDLINE, and full text searches were combined. All analyses were performed according to the intention‐to‐treat method. Only randomised clinical trials studying patients with alcoholic steatosis, alcoholic fibrosis, alcoholic hepatitis and/or alcoholic cirrhosis were included. Interventions encompassed propylthiouracil at any dose versus placebo or no intervention. The trials could be double‐blind, single‐blind or unblinded. Results: Six randomised clinical trials randomising 710 patients demonstrated no significant effects of propylthiouracil versus placebo on mortality (Peto odds ratio (OR) 0.91, 95% confidence interval (CI) 0.59 to 1.40), liver‐related mortality (OR 0.78, CI 0.45 to 1.33), complications to the liver disease (OR 1.14, CI 0.58 to 2.24), and liver histology. Propylthiouracil was associated with a nonsignificant trend toward an increased risk of nonserious adverse events (OR 1.49, CI 0.74 to 2.99) and with the rare occurrence of serious adverse events (leukopenia). Conclusions: This systematic review could not demonstrate any significant effect of propylthiouracil on any clinically important outcomes (mortality, liver‐related mortality, liver complications and liver histology) of patients with alcoholic liver disease.     

Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular carcinoma via a reduction of the inflammatory load from the gut to the liver and inhibition of angiogenesis.