Extracorporeal albumin dialysis (ECAD) may improve severe hepatic encephalopathy (HE) in patients with advanced cirrhosis via the removal of protein or non-protein-bound toxins. A prospective, randomized, controlled, multicenter trial of the efficacy, safety, and tolerability of ECAD using molecular adsorbent recirculating system (MARS) was conducted in such patients. Patients were randomized to ECAD and standard medical therapy (SMT) or SMT alone. ECAD was provided daily for 6 hours for 5 days or until the patient had a 2-grade improvement in HE. HE grades (West Haven criteria) were evaluated every 12 hours using a scoring algorithm. The primary endpoint was the difference in improvement proportion of HE between the 2 groups. A total of 70 subjects [median age, 53; 56% male; 56% HE grade 3; 44% HE grade 4; median model for end-stage liver disease (MELD) 32 (11-50) and CPT 13 (10-15)] were enrolled in 8 tertiary centers. Patients were randomized to ECAD ؉ SMT (n ؍ 39) or SMT alone (n ؍ 31). Groups were matched in demographics and clinical variables. The improvement proportion of HE was higher in ECAD (mean, 34%; median, 30%) versus the SMT group (mean, 18.9%; median, 0%) (P ؍ 0.044) and was reached faster and more frequently than in the SMT group (P ؍ 0.045). H epatic encephalopathy (HE) is a complex neuropsychiatric syndrome commonly seen in patients with advanced liver disease. HE arises from the effects of circulating toxins on cerebral functions. Putative toxic molecules accumulate in patients with liver decompensation because of increased production, portal-systemic shunting, or lack of hepatic detoxification. 1 Patients with advanced cirrhosis and a superimposed acute liver injury often decompensate and present with manifestations of hepatic failure, including worsening HE and coma. 2 .Current therapy for HE includes the use of nonabsorbable disaccharides or poorly absorbable antibiotics, as proposed more than 3 decades ago. 3 However, standard therapy is less effective in patients with severe degrees of liver failure. 4,5 Under these circumstances, the concept of supporting the failing liver for a time while correcting the precipitating event might help patients recover from HE or be stabilized until they receive a liver transplant. 6 Extracorporeal albumin dialysis (ECAD) using the molecular adsorbent recirculating system (MARS) is a new method of hemodiafiltration whereby blood is dialyzed against an albumin-containing solution across a high-flux membrane. 7 The technique allows combined removal of albumin-bound and water-soluble toxins. [8][9][10][11][12] In uncontrolled trials of ECAD using the MARS device, patients had a reduction in ammonia levels, clear-
for the ACTG Protocol A5127 Team Chronic hepatitis B virus (HBV) infection is an important cause of morbidity and mortality in subjects coinfected with HIV. Tenofovir disoproxil fumarate (TDF) and adefovir dipivoxil (ADV) are licensed for the treatment of HIV-1 and HBV infection, respectively, but both have in vivo and in vitro activity against HBV. This study evaluated the anti-HBV activity of TDF compared to ADV in HIV/HBV-coinfected subjects. ACTG A5127 was a prospective randomized, double-blind, placebo-controlled trial of daily 10 mg of ADV versus 300 mg of TDF in subjects with HBV and HIV coinfection on stable ART, with serum HBV DNA > 100,000 copies/mL, and plasma HIV-1 RNA < 10,000 copies/mL. This study closed early based on results of a prespecified interim review, as the primary noninferiority end point had been met without safety issues. Fifty-two subjects were randomized. At baseline, 73% of subjects had a plasma HIV-1 RNA < 50 copies/mL, 86% were HBeAg positive, 94% were 3TC resistant, median serum ALT was 52 IU/L, and 98% had compensated liver disease. The mean time-weighted average change in serum HBV DNA from baseline to week 48 (DAVG 48 ) was ؊4.44 log 10 copies/mL for TDF and ؊3.21 log 10 copies/mL for ADV. There was no difference in toxicity between the 2 treatment arms, with 11 subjects (5 ADV and 6 TDF) experiencing elevations of serum ALT on treatment. In conclusion, over 48 weeks, treatment with either ADV or TDF resulted in clinically important suppression of serum HBV DNA. Both drugs are safe and efficacious for patients coinfected with HBV and HIV.
We evaluated the frequency and severity of muscle cramps, and the effect of dialysate magnesium on muscle cramps in 62 stable ESRD patients on chronic hemodialysis. Each subject was surveyed twice within a 6-month period. A single nephrology fellow conducted all in-person surveys. During the first survey, the patients were dialyzed with dialysate magnesium of 0.75 meq/L (0.375 mmol/L). Prior to the second survey, the dialysate magnesium was increased to 1.0 meq/L (0.50 mmol/L). The severity of cramps was scored on a 1–10 scale, with 10 indicating maximal severity. The number of patients with muscle cramps was significantly lower with dialysate magnesium of 1.0 meq/L (0.50 mmol/L) (56% versus 77%,P=0.02). No significant difference was observed in interdialytic weight gain, intradialytic ultrafiltration, dry weight, or intradialytic hypotension. The mean ± SD severity score of muscle cramps decreased from5.34±3.61to3.89±3.94(P=0.003). Seven of 31 (23%) patients in the group with low dialysate magnesium while 0/20 (0%) patients receiving high magnesium dialysate terminated hemodialysis early due to cramps (P=0.02). Both the number of patients reporting muscle cramps and the severity score decreased with higher dialysate magnesium which contributed to better adherence to hemodialysis treatments.
Cerebral infarction due to fungal arteritis is an uncommon complication of neurosurgical operations and adjuvant immunosuppressive therapy, including long-term steroids. If unrecognized, the neurological deterioration which ensues may be mistreated by increasing the dose of steroids. A case of a 38-year-old Caucasian male who had no obvious immune deficiency or fungal infection prior to a craniotomy for cerebral tumour is described in whom perioperative aspergillus infection resulted in cerebral arteritis and extensive cerebral infarction with a fatal outcome. Long-term steroid therapy used in the management of cerebral tumours may carry an increased risk of systemic or cerebral fungal infection. The possibility of cerebral mycosis (arteritis) and dangers of its non-recognition are highlighted.
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