Recombinant human thrombopoietin (rhTPO) of different dosing regimens for refractory/relapsed primary immune thrombocytopenia: a multicenter, randomized controlled trial and pharmacokinetics study.

Recombinant human TPO (rhTPO) is effective for refractory/relapsed primary immune thrombocytopenia (ITP), but optimal dosing regimen remains elusive. In this multicenter, randomized, controlled trial, a total of 282 adult ITP patients (mean age 47.3 years; 82 men) with a platelet count ≤30 × 109/L or >30 × 109/L with active bleeding randomly received a once daily (QD) subcutaneous injection of 7500 U (n = 64) or 15000 U rhTPO for 14 injections, or 15000 U or 30000 U rhTPO once every other day (QOD) for 7 injections. The primary outcomes included change from baseline in platelet count and total response rate (TRR) on day 14. On day 14, the median increase of platelet count from baseline was the highest in the 15000-U QD group (167.5 × 109/L, interquartile range [IQR] 23.0-295.0 × 109/L), followed by the 30000-U QOD group (57.5 × 109/L, IQR 9.0-190.0 × 109/L) (ANCOVA P < .001; P = .266 with baseline count as a covariate). The TRR on day 14 was also the highest in the 15000-U QD group (63.2%), followed by the 30000-U QOD group (59.7%). The rate of grade 3 and above adverse events did not differ among the four groups. There were no new safety concerns. All 4 regimens are safe and well-tolerated. The 30000-U QOD regimen is practically indistinguishable in efficacy to the 15000-U QD regimen.

What is the context? Relative thrombopoietin deficiency is implicated in primary immune thrombocytopenia (ITP), which is characterized by increased platelet destruction and impaired megakaryopoiesis.Patients who are innately unresponsive to or have relapsed after glucocorticoid treatment have limited treatment options.Recombinant human thrombopoietin (rhTPO) improves treatment response of primary ITP patients when added to high-dose dexamethasone.What is new? This trial sought to identify an optimal dosing regimen of rhTPO for patients who had failed or relapsed after glucocorticoid therapy.Of the 4 regimens, once daily 15000 U rhTPO for 14 injections yielded the greatest median increase in platelet count (167.5 × 10⁹/L) from baseline and attained the highest total response rate on day 14 (63.2%).30000 U rhTPO once every other day for 7 injections was effective in rapidly increasing platelet counts in the first 7 days.All 4 regimens were safe and well-tolerated.What is the impact? The 30000 U rhTPO once every other day regimen may offer an effective and safe regimen with less frequent injections, but future trials with longer follow-up are needed.

Baud rate and shaping blocklength effects on the nonlinear performance of super-symbol transmission.

In this paper we study the nonlinear performance of super-symbol (SUP) transmission. We analyze the spectral dip, a unique feature of SUP, as a function of various system parameters and discuss how this dip and the associated nonlinear benefit would vary with different baud rates and shaping blocklengths. We then conduct simulations to verify our analysis, by which we confirm that the SUP performance can be optimized via a judicious choice on the baud rate and/or blocklength. Furthermore, a nonlinear noise study confirms that the nonlinear benefit of SUP mainly comes from its significant nonlinear phase noise (NLPN) reduction.

Experimental demonstration of super-symbol transmission for improved fiber nonlinearity tolerance.

We experimentally verified the enhanced nonlinear tolerance of probabilistic shaping (PS) 64QAM super symbol (SUP) transmission over both dispersion uncompensated and compensated standard single mode fiber (SSMF) links. PS-64QAM with SUP is found to provide ∼0.51- and ∼1.6-dB gains in OSNR over PS-64QAM with traditional probabilistic amplitude shaping, after ∼1000-km uncompensated and 320-km compensated links, respectively.

Mitigation of optical multipath interference impact for directly detected PAMn system.

This paper investigates solutions for mitigating multipath interference (MPI) impact for intensity modulation direct detection systems, particularly for PAM4 systems. We propose a scheme that uses a high pass filter (HPF) at the receiver to remove the MPI induced carrier-carrier beat noise and therefore improve the MPI tolerance. The scheme has been verified via theoretical analysis, numerical simulation, and experiment. For a typical optical transmitter based on Mach-Zehnder modulator (MZM) without frequency chirp, over 5dB MPI tolerance can be improved for 106.4Gb/s PAM4 by using the proposed scheme. Investigation was also extended to electro-absorption modulated laser (EML) and directly modulated laser (DML) based optical transmitters. Results show that transient chirping in EML reduces the effectiveness of proposed MPI mitigation scheme. For EML with chirp factor smaller than 1.5, MPI tolerance gain of 2dB is still achievable. However, the scheme is ineffective for typical DML where the adiabatic chirp significantly broadened the laser linewidth.

200G self-homodyne detection with 64QAM by endless optical polarization demultiplexing.

This paper investigates the self-homodyne detection system with orthogonal polarization between pilot and signal (oSHD) through optical polarization demultiplexing of carrier and signal at receiver. Compared to digital demultiplexing, optical demultiplexing provides around a 0.9dB benefit in receiver sensitivity. The impact of crosstalk due to optical demultiplexing has been investigated in terms of carrier-to-signal power ratio, and delay between signal and carrier. Results show that the oSHD system is very tolerant to crosstalk, with a negligible penalty for crosstalk up to -22dB. Experiments were carried out to evaluate the system performance, including polarization tracking performance, long term stability, bit error rate performance, and tolerance to laser linewidth and delay between signal and pilot. 41Gbaud 64QAM oSHD with 200Gb/s net data rate has been realized by using the scheme with receiver sensitivity better than -4dBm, providing a promising candidate solution for 800Gb/s Ethernet.

Transmission method of improved fiber nonlinearity tolerance for probabilistic amplitude shaping.

For probabilistic amplitude shaping (PAS), we propose a super-symbol transmission method that improves fiber nonlinearity tolerance. A simple fiber nonlinearity low-pass filtering model, as well as its interaction with the spectral dip of signal's intensity waveform, is provided to explain the origin of this nonlinear benefit. With 25-GHz-spaced, 26 × 22.5 GBaud dual-polarized PAS-64 quadrature amplitude modulation (QAM) signals transmitted over 12 spans of 80-km standard single mode fiber (SSMF), the proposed method is found to provide ∼0.15-dB gain over the previous finite-blocklength method with intra-DM pairing, ∼0.26-dB gain over finite-blocklength method with inter-DM pairing, and ∼0.44-dB benefit over the traditional method, all with a feasible blocklength at 200.

A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy.

The aim of this study was to determine the safety and efficacy of recombinant human thrombopoietin (rhTPO) for the management of immune thrombocytopenia (ITP) during pregnancy. Pregnant patients with ITP were enrolled in the study if they had a platelet count less than 30 × 109/L, were experiencing bleeding manifestations, had failed to respond to corticosteroids and/or intravenous immunoglobulin (IVIG), and had developed refractoriness to platelet transfusion. Thirty-one patients received rhTPO at an initial dose of 300 U/kg once daily for 14 days. Twenty-three patients responded (74.2%), including 10 complete responders (>100 × 109/L) and 13 responders (30-100 × 109/L). It appears that rhTPO ameliorated the bleeding symptoms remarkably, even in the nonresponders. rhTPO was well tolerated. Dizziness, fatigue, and pain at an injection site were reported in 1 patient each. No congenital disease or developmental delays were observed in the infants in a median follow-up of 53 (range, 39-68) weeks. In conclusion, rhTPO is a potentially safe and effective treatment choice for patients with ITP during pregnancy. Our work has paved the way for further study on the clinical application of rhTPO and other thrombopoietic agents for the management of ITP during pregnancy. This study is registered at www.clinicaltrials.gov as NCT02391272.

Phylogenetic analysis of H7N9 avian influenza virus based on a novel mathematical descriptor.

A new mathematical descriptor was proposed based on 3D graphical representation. Using the method, we construct the phylogenetic trees of nine proteins of H7N9 influenza virus to analyze the originated source of H7N9. The results show that the evolution route of H7N9 avian influenza is from America through Europe to Asia. Furthermore, two samples collected from environment in Nanjing and Zhejiang and one sample collected from chicken are the sources of H7N9 influenza virus that infected human in China.