Growth modulation index as metric of clinical benefit assessment among advanced soft tissue sarcoma patients receiving trabectedin as a salvage therapy.

BACKGROUND: The growth modulation index (GMI) is the ratio of time to progression with the nth line (TTP(n)) of therapy to the TTP(n)(-1) with the n-1th line. GMI >1.33 is considered as a sign of activity in phase II trials. PATIENTS AND METHODS: This retrospective analysis evaluated the concordance between the GMI and the efficacy outcomes in 279 patients with advanced soft tissue sarcoma (ASTS) treated with trabectedin 1.5 mg/m² (24-h infusion every 3 weeks) in four phase II trials. RESULTS: One hundred and forty-two (51%) patients received one prior line and 137 ≥ 2 lines. The median TTP(n) was 2.8 months (range 0.2-26.8), whereas the median TTP(n)(-1) was 4.0 months (0.3-79.5). The median GMI was 0.6 (0.0-14.4). Overall, 177 patients (63%) had a GMI <1; 21 (8%) a GMI equal to 1-1.33 and 81 (29%) a GMI >1.33, which correlated with the median overall survival in those patients (9.1, 13.9 and 23.8 months, respectively, P = 0.0005). A high concordance rate between the GMI and response rate (P < 0.0001) and progression-free survival (PFS, P < 0.0001) was observed. Good performance status (PS) was the only factor associated with GMI >1.33 (PS = 0; P < 0.04). CONCLUSIONS: A high GMI was associated with favorable efficacy outcomes in patients treated with trabectedin. Further research is needed to assess GMI as an indicator in this setting.

Numerical comparison between conventional dispersion compensating fibers and photonic crystal fibers as lumped Raman amplifiers.

In this paper we discuss the use of photonic crystal fibers (PCFs) as discrete devices for simultaneous wideband dispersion compensation and Raman amplification. The performance of the PCFs in terms of gain, ripple, optical signal-to-noise ratio (OSNR) and required fiber length for complete dispersion compensation is compared with conventional dispersion compensating fibers (DCFs). The main goal is to determine the minimum PCF loss beyond which its performance surpasses a state-of-the-art DCF and justifies practical use in telecommunication systems.

Design methodology for multi-pumped discrete Raman amplifiers: case-study employing photonic crystal fibers.

This paper proposes a new design methodology for discrete multi-pumped Raman amplifier. In a multi-objective optimization scenario, in a first step the whole solution-space is inspected by a CW analytical formulation. Then, the most promising solutions are fully investigated by a rigorous numerical treatment and the Raman amplification performance is thus determined by the combination of analytical and numerical approaches. As an application of our methodology we designed an photonic crystal fiber Raman amplifier configuration which provides low ripple, high gain, clear eye opening and a low power penalty. The amplifier configuration also enables to fully compensate the dispersion introduced by a 70-km singlemode fiber in a 10 Gbit/s system. We have successfully obtained a configuration with 8.5 dB average gain over the C-band and 0.71 dB ripple with almost zero eye-penalty using only two pump lasers with relatively low pump power.

[Diagnostic imaging in Lemierre's+ syndrome]. / Diagnóstico por imagen en el síndrome de Lemierre.

BACKGROUND: The Lemierre syndrome is a septic picture with jugular thrombophlebitis and secondary septic embolisms usually produced by Fusobacterium necrophorum. In previous reports published in the literature, imaging techniques are seldom referred to report the presence of jugular thrombophlebitis. A case of the Lemierre syndrome is presented with the aim of calling attention to this process and its current diagnostic possibilities. METHODS: The case of a patient who was diagnosed of having a Lemierre syndrome with sepsis by Fusobacterium is presented, with radiologic pulmonary embolisms. The echo-Doppler exam showed the presence of internal jugular involvement in absence of signs and symptoms leading to suspicion. A review of 6 cases is also made with special attention being given to the data on jugular vein involvement. RESULTS: Only in 2 of the 6 patients reviewed were imaging techniques used on the internal jugular view (in one 2D echography and in the other computerized axial tomography) with the diagnosis being performed on the base of symptomatic and physical exam data in the remaining 4 cases. CONCLUSIONS: The Lemierre syndrome should be suspect in all patients with bacteremia by Fusobacterium and radiologic imaging of pulmonary embolism, even in the absence of signs and symptoms of oropharyngeal and jugular involvement. Modern imaging techniques, particularly echo-Doppler, may play an important diagnostic role.

[Myopathy and zidovudine]. / Miopatía y zidovudina.

BACKGROUND: The aim of this study was to evaluate the frequency of appearance of myopathy in a group of patients treated with zidovudine. METHODS: A prospective study of 37 patients with positive serology for HIV treated over 180 days with zidovudine was carried out with evaluation of the clinical history, physical examination and analytical data. RESULTS: The initial mean value of creatine kinase of 76.4 U/l and 83.3 U/l following 6 months of treatment was not statistically significant. Of the 37 patients, 2 (5.4%) showed no variations in CK values, while in 4 (10.8%) there was a decrease and in 30 (81%) an increase. There was an elevation in 11 of the 15 patients (73%) who received doses equal to or lower than 90 g, 11 out of 13 (84.6%) of those who received between 90 and 145 g and 8 out of 8 (100%) of those having received doses higher than 145 g. This increase was minimum in 27 cases (92%) and important with final values of pathologic CK in 3 (8%). Two patients (5.4%) developed clinical manifestations. CONCLUSIONS: Not only the frequency and range of creatine kinase elevation but also the appearance of clinical manifestations in this study are lower than those found in the literature, probably because of the relation with the use of lower doses of zidovudine. These results do not demonstrate any relation with sex, age, risk group for the immunodeficiency status.

Liposomal amphotericin B and amphotericin B-deoxycholate show different immunoregulatory effects on human peripheral blood mononuclear cells.

Conventional preparations of amphotericin B (AmB) at established therapeutic doses are known to increase nonspecific immune responses. It remains to be established whether higher doses of the less toxic liposomal preparation of AmB maintains a beneficial effect on the immune response to fungal infections. Examination of the effect of treatment of human peripheral blood mononuclear cells from healthy subjects with various doses of both liposomal AmB (L-AmB) and deoxycholate AmB (d-AmB) on proliferation, cell viability, and percentage of apoptosis demonstrated that, although both L-AmB and d-AmB at low doses significantly increased nonspecific proliferative responses, L-AmB, but not d-AmB, treatment maintained this beneficial effect at higher doses. High doses of d-AmB, but not L-AmB, resulted in significantly decreased cell viability and increased apoptosis. This study provides further evidence in healthy human subjects for choosing L-AmB over conventional preparations in the clinical treatment of fungal infections requiring systemic high-dose treatment with AmB.