Imaging of the medial rectus muscle predicts the development of optic neuropathy in thyroid eye disease.

Goal of the study was to evaluate bony orbit remodeling and extraocular muscle (EOM) volume in thyroid eye disease (TED) and their role as predicting factors for development of dysthyroid optic neuropathy (DON). Orbital computed tomography of 92 patients with TED with (76 orbits) or without DON (98 orbits) were retrospectively evaluated. Orbits (n = 40) of subjects without TED served as controls. Measurements of the bony orbit as well as EOM volume were incorporated into a generalized linear mixed model to predict DON. The angle of the medial orbital wall was significantly smaller (p < 0.001) in patients with TED (- 2.3 ± 3.6°) compared to patients with TED + DON (1.0 ± 4.1°). Both groups differed significantly from controls (- 4.2 ± 2.7°). Bowing of the medial orbital wall correlated positively with muscle volume (r = 0.564; p < 0.001). Total EOM volume was significantly larger in TED + DON (7.6 ± 2.5cm3) compared to TED only (5.6 ± 3.0cm3; p < 0.001) or controls (2.6 ± 0.5cm3). Multivariate analysis revealed the medial rectus muscle volume (TED: 1.06 ± 0.48cm3 vs. TED + DON: 2.16 ± 0.84cm3) as the strongest predictor, achieving a specifity of 86.7% and a sensitivity of 73.7% in diagnosing DON in univariate analysis. Though characterized by a wide range of variability, increased medial rectus muscle volume is the strongest predictor for DON in our patient cohort with TED when analyzing a single muscle.

Stage-adapted treatment of HIV-associated Hodgkin lymphoma: results of a prospective multicenter study.

PURPOSE: Although the outcome of patients with HIV-related Hodgkin lymphoma (HIV-HL) has markedly improved since the introduction of combined antiretroviral therapy, standard therapy is still poorly defined. This prospective study investigates a stage- and risk-adapted treatment strategy in patients with HIV-HL. PATIENTS AND METHODS: Patients with early favorable HIV-HL received two to four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy of involved-field (IF) radiation. In patients with early unfavorable HIV-HL, four cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP baseline) or four cycles of ABVD + 30 Gy of IF radiation were administered. Six to eight cycles of BEACOPP baseline were given in patients with advanced-stage HIV-HL. In patients with advanced HIV infection, BEACOPP was replaced with ABVD. RESULTS: Of 108 patients (including eight female patients) included in the study, 23 (21%) had early favorable HL, 14 (13%) had early unfavorable HL, and 71 (66%) had advanced-stage HL. The median CD4 count at HL diagnosis was 240/µL. The complete remission rates for patients with early favorable, early unfavorable, and advanced-stage HL were 96%, 100%, and 86%, respectively. The 2-year progression-free survival of the entire study population was 91.7%. Eleven patients (11%) have died, and treatment-related mortality was 5.6%. The 2-year overall survival rate was 90.7% with no significant difference between early favorable (95.7%), early unfavorable (100%), and advanced-stage HL (86.8%). CONCLUSION: In patients with HIV-HL, stage- and risk-adapted treatment is feasible and effective. The prognosis for patients with HIV-HL may approach that of HIV-negative patients with HL.

Saquinavir, nelfinavir and M8 pharmacokinetics following combined saquinavir, ritonavir and nelfinavir administration.

OBJECTIVES: This study evaluated the steady-state pharmacokinetic interaction between ritonavir-boosted saquinavir and nelfinavir. METHODS: Open label, multiple-dose, two parallel-groups, single crossover study conducted in 24 HIV-infected patients (12 in each group). Patients in the nelfinavir group added saquinavir/ritonavir, 1000/100 mg twice daily to their ongoing stable treatment regimen consisting of nelfinavir, 1250 mg twice daily and two nucleoside reverse transcriptase inhibitors (NRTIs). Patients in the saquinavir group added nelfinavir, 1250 mg twice daily to their ongoing stable treatment regimen consisting of saquinavir/ritonavir, 1000/100 mg twice daily and two NRTIs. Pharmacokinetic assessments were performed before and 7 days after the start of combined treatment with nelfinavir/saquinavir/ritonavir. Blood samples were collected before and 1, 2, 3, 4, 6, 8, 10 and 12 h after dosing for measurement of nelfinavir, the nelfinavir metabolite M8 and saquinavir using liquid chromatography tandem mass spectrometry (LC-MS/MS). RESULTS: The addition of saquinavir/ritonavir to the nelfinavir-containing regimen resulted in significant increases in the M8 pharmacokinetic parameters AUC(0-12), Cmax and C12; geometric mean ratios (90% confidence intervals) of 2.25 ng.h/mL (1.47-3.44), 1.74 ng/mL (1.25-2.40) and 4.21 ng/mL (2.10-8.47), respectively. The intra-individual changes in nelfinavir and saquinavir concentrations were highly variable. Statistical analysis could not discard a relevant interaction but includes the possibility that some parameters may be halved, others more than doubled. At the same time the analysis failed to show any directed change. CONCLUSIONS: The co-administration of nelfinavir and saquinavir/ritonavir leads to unpredictable changes in concentrations of both drugs. It is unclear whether the increased concentrations of M8 are associated with a clinical benefit.