Improved freedom from rejection after a loading dose of sirolimus

BACKGROUND: Sirolimus (SIR) in combination with cyclosporine reduces the incidence of acute rejection in renal transplant recipients. Limited data are available regarding SIR in combination with tacrolimus (TAC). METHODS: A single-center, retrospective review of renal transplant recipients receiving SIR, TAC, and corticosteroids postoperatively was conducted. A total of 118 consecutive renal transplant recipients were included on the basis of availability of day 1 SIR dose information. Seventy-seven patients received an SIR loading dose (SIR-LD) immediately posttransplantation, and 41 patients did not (SIR no loading dose [SIR-NLD]). RESULTS: The two groups showed similar demographic and transplant characteristics. SIR doses and trough levels were significantly higher in the SIR-LD patients at 1 and 7 days posttransplantation; however, no differences occurred beyond day 7. Patients receiving an SIR-LD experienced significantly better freedom from rejection at 1, 3, and 6 months posttransplantation (P<0.05). This rejection benefit in the SIR-LD group was independent of donor source and use of antibody induction. SIR-LD patients experienced fewer serious infections (12% SIR-LD vs. 27% SIR-NLD, P=0.04) and a lower incidence of delayed graft function (21% SIR-LD vs. 39% SIR-NLD, P<0.05). No significant differences in serum creatinine, hemoglobin, and platelet counts occurred in the first 180 days posttransplantation, but the patients in the SIR-NLD group experienced lower hemoglobin levels at day 30 than those in the SIR-LD group (10.8 g/dL SIR-LD vs. 9.7 g/dL SIR-NLD, P=0.03). CONCLUSION: SIR-LD significantly improves early posttransplantation freedom from rejection in renal transplant recipients without increasing other complications.     

Symptomatic antiepileptic drug associated vitamin D deficiency in noninstitutionalized patients: an under-diagnosed disorder

Four noninstitutionalized patients, 4 months - 51 years old, presented out of 421 patients with epilepsy seen within a period of 2 years with serious symptoms of vitamin D deficiency secondary to chronic antiepileptic drug therapy. Presenting symptoms included exacerbation of seizure activity, status epilepticus, carpopedal spasms, fractures, osteomalacia, and rickets. All had low serum calcium and low vitamin D levels. Our experience supports the practice of screening patients on chronic antiepileptic drug therapy for vitamin D abnormalities.     

Synaptic plasticity in mammalian photoreceptors prepared as sheets for retinal transplantation

PURPOSE: To investigate systematically the early morphologic changes in axon terminals of adult mammalian rod and cone photoreceptors prepared as a sheet for subretinal transplantation. METHODS: An in vitro system was designed to maintain adult porcine retinas for up to 48 hours. Photoreceptor sheets, prepared by vibratome sectioning, and full-thickness retinas were cultured at temperatures similar to those in pretransplantation storage (4 degrees C) and after transplantation (37 degrees C). Changes in the outer nuclear and outer plexiform layers were analyzed, using immunohistochemistry, laser scanning confocal microscopy, and image analysis. RESULTS: Morphologic changes were observed in photoreceptor sheets as early as 10 minutes after incubation. The most significant change was the retraction of photoreceptor axons and terminals toward their cell bodies. Retraction was temperature dependent, being exacerbated at 37 degrees C compared with 4 degrees C, at its maximum by 24 hours of culture, and present in sheets obtained from both superior and inferior retina. The cause of this movement was not preparation techniques associated with vibratome sectioning or gelatin removal. Retraction was also present in full-thickness neural retina incubated at 37 degrees C. Reduction in outer nuclear layer cell counts and thickness were also evident in these preparations, primarily in photoreceptor sheets. CONCLUSIONS: Adult photoreceptor sheets, a potential graft preparation for retinal transplantation, show a rapid retraction of axon terminals toward the cell bodies during culture. Although retraction may impede synaptic integration after transplantation, this intrinsic plasticity could be redirected to stimulate graft-host interaction.     

Bladder irrigation using hydrogen peroxide for clot evacuation

Evacuation of clot from the bladder by irrigation can be difficult when significant clot burden or organized clot exists. We describe a novel technique for the evacuation of clot from the bladder using irrigation containing hydrogen peroxide that facilitated clot removal.     

Pegylated liposomal doxorubicin, vincristine, and dexamethasone provide significant reduction in toxicity compared with doxorubicin, vincristine, and dexamethasone in patients with newly diagnosed multiple myeloma: a Phase III multicenter randomized trial

BACKGROUND: Pegylated liposomal doxorubicin has pharmacologic and safety advantages over conventional doxorubicin. METHODS: For this noninferiority trial, 192 patients with newly diagnosed, active multiple myeloma were randomized to receive either combined pegylated liposomal doxorubicin (40 mg/m(2)) and vincristine (1.4 mg/m(2); maximum, 2.0 mg) as an intravenous infusion on Day 1 plus reduced-dose dexamethasone (40 mg) orally on Days 1-4 (DVd) (n = 97 patients) or combined vincristine (0.4 mg per day) and conventional doxorubicin (9 mg/m(2) per day) as a continuous intravenous infusion on Days 1-4 plus reduced-dose dexamethasone (VAd) (n = 95 patients) for at least 4 cycles. Treatment was repeated every 4 weeks until patients either achieved maximal response, disease progression, or unacceptable toxicity or underwent transplantation. The primary endpoints were response and toxicity. RESULTS: Objective response rates (DVd, 44%; VAd, 41%), progression-free survival (hazard ratio, 1.11; P = 0.69), and overall survival (hazard ratio, 0.88; P = 0.67) were similar between the treatment groups. However, DVd was associated with significantly less Grade 3/4 neutropenia or neutropenic fever (10% vs. 24%; P = 0.01), a lower incidence of sepsis, and less antibiotic use. Compared with VAd, DVd also significantly decreased the need for central venous access (P < 0.0001) and growth-factor support (P = 0.03) and resulted in less alopecia (20% vs. 44%; P < 0.001) but more hand-foot syndrome (25% vs. 1%; P < 0.001), mainly Grade 1/2. CONCLUSIONS: The DVd regimen demonstrated similar efficacy with less toxicity and supportive care compared with VAd, which should improve clinical utility and optimize the opportunity for transplantation.     

Probabilistic reporting of EUS-FNA cytology: Toward improved communication and better clinical decisions

BACKGROUND: The objectives of this study were to determine threshold probabilities needed to perform endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and those needed to treat patients suspected of having malignancy and then to compare these thresholds to the pre- and posttest probabilities of malignancy associated with benign, atypical, suspicious, and malignant diagnoses. The goal was to aid endoscopists in making appropriate clinical decisions based on both quantitative and qualitative approaches. METHODS: The study included 633 consecutive patients. A decision tree was constructed to estimate the "treatment" threshold. Using treatment threshold and likelihood ratios, the authors determined the "no-test-test" and "test-treatment" thresholds. Pretest probability was compared with no-test-test and test-treatment thresholds, and the post-EUS-FNA probability of malignancy for each diagnostic category with the treatment threshold. Results were stratified by lesion site, lesion size, and cytopathologist. RESULTS: EUS-FNA has a wide range of pretest probabilities within which it could be performed (0.06-0.98). The posttest probabilities for malignancy, 0.99 (95% confidence interval [CI], 0.967-0.996) and 0.09 (95% CI, 0.057-0.126), after a positive or a negative result, respectively, were significantly different from the treatment threshold but not those of suspicious, 0.92 (95% CI, 0.767-0.994) diagnosis. The posttest probability of atypical diagnosis, 0.60 (95% CI, 0.407-0.772), was not significantly different from that of pretest probability. Results did not vary by lesion size, organ site, or cytopathologist. CONCLUSION: The authors demonstrated the uncertainty associated with EUS-FNA diagnostic categories and used the threshold approach to qualify quantitatively the decision to perform EUS-FNA and the decision to treat patients suspected of having malignancy.