Bone mineral density before and after OLT: long-term follow-up and predictive factors.

Fracturing after liver transplantation (OLT) occurs due to the combination of preexisting low bone mineral density (BMD) and early posttransplant bone loss, the risk factors for which are poorly defined. The prevalence and predictive factors for hepatic osteopenia and osteoporosis, posttransplant bone loss, and subsequent bone gain were studied by the long-term posttransplant follow-up of 360 consecutive adult patients with end-stage primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). Only 20% of patients with advanced PBC or PSC have normal bone mass. Risk factors for low spinal BMD are low body mass index, older age, postmenopausal status, muscle wasting, high alkaline phosphatase and low serum albumin. A high rate of spinal bone loss occurred in the first 4 posttransplant months (annual rate of 16%) especially in those with younger age, PSC, higher pretransplant bone density, no inflammatory bowel disease, shorter duration of liver disease, current smoking, and ongoing cholestasis at 4 months. Factors favoring spinal bone gain from 4 to 24 months after transplantation were lower baseline and/or 4-month bone density, premenopausal status, lower cumulative glucocorticoids, no ongoing cholestasis, and higher levels of vitamin D and parathyroid hormone. Bone mass therefore improves most in patients with lowest pretransplant BMD who undergo successful transplantation with normal hepatic function and improved gonadal and nutritional status. Patients transplanted most recently have improved bone mass before OLT, and although bone loss still occurs early after OLT, these patients also have a greater recovery in BMD over the years following OLT.     

Induction of immune tolerance in patients with hemophilia A and inhibitors treated with porcine VIIIC by home therapy

Home therapy with porcine factor VIIIC was safe and effective when administered to five hemophilic patients over periods of 8 1/2, 6, 4, 3 1/2, and 2 years. No significant transfusion reactions occurred. Before treatment with porcine factor VIIIC, all five had high-level, high- responding anti-human VIIIC inhibitors initially lacking anti-porcine factor VIIIC activity. Although specific anti-porcine VIIIC inhibitors arose in all patients, these were generally transient, and only one patient became refractory to treatment. We believe that porcine factor VIIIC is the treatment of choice in patients whose inhibitors do not cross-react. All five patients lost their original anti-human VIIIC inhibitors after starting treatment with porcine VIIIC, permitting the reintroduction of human VIIIC in three of them. There has been no recurrence of anti-human VIIIC inhibitor activity during 2 to 3 years of regular treatment with human VIIIC in these patients. This suggests that tolerance to human VIIIC has arisen as a result of treatment with porcine VIIIC. Porcine VIIIC may have a role in the desensitization of some factor VIIIC inhibitor patients.     

The treatment of bleeding in hemophilic patients with inhibitors with recombinant factor VIIa

Recombinant factor VIIa (rFVIIa) has proven efficacy in the treatment of patients with alloantibodies and autoantibodies to factors VIII and IX. More than 80% of over 2,000 reported bleeding episodes treated with rFVIIa have been controlled in a variety of clinical circumstances. Its theoretical lack of activation of the coagulation system prompted many clinicians to undertake elective surgical procedures using rFVIIa in addition to on-demand treatment of minor bleeding episodes. Hemostatic efficacy has been good for most of these surgical procedures, without serious adverse events. rFVIIa is considered a useful, safe, and effective treatment for bleeding in patients with anti-factor VIII (FVIII) and anti-factor IX (FIX) inhibitors. However, the optimal dose for various clinical situations has yet to be established and requires further investigation. Laboratory monitoring of treatment using plasma FVIIa measurements should be better standardized. Despite the relatively high cost of this new drug, rFVIIa represents a major therapeutic advance in the treatment of hemophilic patients with inhibitors.     

Treatment of chronic mucocutaneous candidosis with ketoconazole: a study of 12 cases

Twelve patients with chronic mucocutaneous candidosis were treated orally with ketoconazole (doses, 200-400 mg daily) for a mean period of six months. Seven of the patients had one of the following abnormalities: congenital endocrinopathy syndrome, an autosomal recessive or autosomal dominant defect in which candidosis is not associated with endocrinopathy, or the malabsorption syndrome. All patients had fungal infections of the mouth, and 11 had onychomycosis. Two patients were also infected with dermatophytes. At the end of treatment, 10 patients were cured of oral infection, and 11 with nail infections showed significant improvement. Marked improvement of hand and foot infections was also recorded. Patients infected with dermatophyte fungi had the poorest responses to therapy. The mean (+/- SD) MIC for isolates of Candida albicans from eight patients was 0.95 (+/- 0.78) microgram/ml. Clinical and biochemical monitoring showed no toxicity, and no resistant fungi emerged during treatment. Results of this initial study of ketoconazole for treatment of severe and recalcitrant superficial infections indicate the need for further assessment of this drug, which appears to offer a simple, nontoxic, and effective treatment of fungal infections.     

Duloxetine for the long-term treatment of Major Depressive Disorder in patients aged 65 and older: an open-label study

Background  

Late-life depression is a common, chronic and recurring disorder for which guidelines recommend long-term therapy. The safety and efficacy of duloxetine for the treatment of major depressive disorder (MDD) were evaluated using data from elderly patients (age ≥ 65 years; n = 101) who participated in a large, multinational, open-label study.