Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Immune profiling of lupus miliaris disseminatus faciei and successful management with anti-tumour necrosis factor therapy.

Lupus miliaris disseminatus faciei (LMDF) is a chronic inflammatory dermatosis of unknown aetiology, most often seen in young adults. Although many treatments for LMDF exist, treatment guidelines have not been developed, and response to therapy is generally unpredictable. We present the results of transcriptomic analysis of LMDF lesional skin, which revealed a variety of differentially expressed genes linking LMDF to alterations in innate and adaptive T helper 1 immunity. Immunohistochemical analysis was also performed, identifying similar changes in T-cell immune responses. Given evidence for increased tumour necrosis factor (TNF) pathway activity, our patient, who had previously been refractory to multiple treatments, was initiated on TNF inhibitor therapy with excellent response. This characterization of the LMDF immune response may lead to improved treatment of this condition.

Transmission performance improvement using random DFB laser based Raman amplification and bidirectional second-order pumping.

We demonstrate that a distributed Raman amplification scheme based on random distributed feedback (DFB) fiber laser enables bidirectional second-order Raman pumping without increasing relative intensity noise (RIN) of the signal. This extends the reach of 10 × 116 Gb/s DP-QPSK WDM transmission up to 7915 km, compared with conventional Raman amplification schemes. Moreover, this scheme gives the longest maximum transmission distance among all the Raman amplification schemes presented in this paper, whilst maintaining relatively uniform and symmetric signal power distribution, and is also adjustable in order to be highly compatible with different nonlinearity compensation techniques, including mid-link optical phase conjugation (OPC) and nonlinear Fourier transform (NFT).

Dual-polarization multi-band optical OFDM transmission and transceiver limitations for up to 500 Gb/s uncompensated long-haul links.

A number of critical issues for dual-polarization single- and multi-band optical orthogonal-frequency division multiplexing (DP-SB/MB-OFDM) signals are analyzed in dispersion compensation fiber (DCF)-free long-haul links. For the first time, different DP crosstalk removal techniques are compared, the maximum transmission-reach is investigated, and the impact of subcarrier number and high-level modulation formats are explored thoroughly. It is shown, for a bit-error-rate (BER) of 10(-3), 2000 km of quaternary phase-shift keying (QPSK) DP-MB-OFDM transmission is feasible. At high launched optical powers (LOP), maximum-likelihood decoding can extend the LOP of 40 Gb/s QPSK DP-SB-OFDM at 2000 km by 1.5 dB compared to zero-forcing. For a 100 Gb/s DP-MB-OFDM system, a high number of subcarriers contribute to improved BER but at the cost of digital signal processing computational complexity, whilst by adapting the cyclic prefix length the BER can be improved for a low number of subcarriers. In addition, when 16-quadrature amplitude modulation (16QAM) is employed the digital-to-analogue/analogue-to-digital converter (DAC/ADC) bandwidth is relaxed with a degraded BER; while the 'circular' 8QAM is slightly superior to its 'rectangular' form. Finally, the transmission of wavelength-division multiplexing DP-MB-OFDM and single-carrier DP-QPSK is experimentally compared for up to 500 Gb/s showing great potential and similar performance at 1000 km DCF-free G.652 line.

Impact ionization-induced bistability in CMOS transistors at cryogenic temperatures for capacitorless memory applications.

Cryogenic operation of complementary metal oxide semiconductor (CMOS) silicon transistors is crucial for quantum information science, but it brings deviations from standard transistor operation. Here, we report on sharp current jumps and stable hysteretic loops in the drain current as a function of gate voltage V G for both n- and p-type commercial-foundry 180-nm-process CMOS transistors when operated at voltages exceeding 1.3 V at cryogenic temperatures. The physical mechanism responsible for the device bistability is impact ionization charging of the transistor body, which leads to effective back-gating of the inversion channel. This mechanism is verified by independent measurements of the body potential. The hysteretic loops, which have a >107 ratio of high to low drain current states at the same V G, can be used for a compact capacitorless single-transistor memory at cryogenic temperatures with long retention times.

Primary cytomegalovirus ileitis complicated by massive gastrointestinal haemorrhage in a patient with steroid refractory Crohn's disease.

A young man with known steroid refractory terminal ileal Crohn's disease developed torrential gastrointestinal bleeding necessitating an emergency ileal resection. Serology was indicative of primary cytomegalovirus (CMV) infection and this was confirmed with histopathology of the resected ileum. We highlight the difficulty in clinical practice of distinguishing between CMV infection and CMV disease as well as the different investigations available to aid in the diagnosis of pathogenic CMV disease.

Hydroxylation of pentamidine by rat liver microsomes.

The antiprotozoal/antifungal drug pentamidine [1,5-bis(4-amidinophenoxy)pentane] has been recently shown to be metabolized by rat liver fractions to at least six putative metabolites as detected by high-performance liquid chromatography. Two minor metabolites have been previously identified as N-hydroxypentamidine and N,N'-dihydroxypentamidine. In this study, the two major microsomal metabolites have been identified as the 2-pentanol and 3-pentanol analogs of pentamidine [1,5-di(4-amidinophenoxy)-2-pentanol; and 1,5-bis(4-amidinophenoxy)-3-pentanol]. As well, a seventh putative metabolite has been discovered and identified as para-hydroxybenzamidine, a fragment of the original drug. Whereas the cytochromes P-450 have been demonstrated as the enzyme system responsible for pentamidine metabolism, hydroxylation of the drug was not inducible by phenobarbital, beta-naphthoflavone, clofibrate, isosafrole, pregnenolone-16 alpha-carbonitrile, ethanol or pentamidine pretreatment of rats. The kinetics of the production of the two major microsomal metabolites has been determined as Km = 56 +/- 19 microM and Vmax = 126 +/- 21 pmol/min/mg microsomal protein for the 2-pentanol analog, and Km = 28 +/- 0.28 microM and Vmax = 195 +/- 2.4 pmol/min/mg microsomal protein for the 3-pentanol analog. Therefore, the mixed-function oxidases readily convert pentamidine to hydroxylated metabolites, but exactly which isozyme(s) of cytochrome P-450 is responsible is not clear.