Laser Speckle Contrast Imaging Guides Needling Treatment of Vascular Complications from Dermal Fillers.

BACKGROUND: Although laser Doppler imaging (LDI) accurately delineates a hypoperfused area to help target hyaluronidase treatment, laser speckle contrast imaging (LSCI) is more appropriate for assessing microvascular hemodynamics and has greater reproducibility than LDI. This study investigated the use of LSCI in the evaluation and treatment of six patients who developed vascular complications after facial dermal filler injections. METHODS: The areas of vascular occlusion were accurately defined in real time by LSCI and were more precise than visual inspections or photographic evidence for guiding needling and hyaluronidase treatment. RESULTS: All patients had achieved satisfactory outcomes as early as Day 2 of treatment and no procedure-related complications were reported after a median follow-up of 9.5 (7-37) days. CONCLUSION: LSCI accurately and noninvasively delineated vascular occlusions in real time among patients experiencing complications of facial dermal filler injections. Moreover, LSCI was more accurate than visual and photographic evaluations. Clinicians can use LSCI to reliably follow-up therapeutic outcomes after salvage interventions for vascular occlusions. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficacy and safety of baricitinib in combination with topical corticosteroids in paediatric patients with moderate-to-severe atopic dermatitis with an inadequate response to topical corticosteroids: results from a phase III, randomized, double-blind, placebo-controlled study (BREEZE-AD PEDS).

BACKGROUND: Baricitinib, an oral selective Janus kinase (JAK)1/JAK2 inhibitor, is approved in many countries for moderate-to-severe atopic dermatitis (AD) in adults who are candidates for systemic therapy. OBJECTIVES: To evaluate the efficacy and safety of three doses of baricitinib in combination with low-to-moderate potency topical corticosteroids in paediatric patients with moderate-to-severe AD. METHODS: Patients (aged 2 to < 18 years) were randomized (1 : 1 : 1 : 1) to once-daily baricitinib low dose (1 mg equivalent), medium dose (2 mg equivalent), high dose (4 mg equivalent) or placebo for 16 weeks. The primary endpoint was the proportion of patients achieving a validated Investigator Global Assessment® (vIGA-AD) of 0/1 with a ≥ 2-point improvement at week 16. Key secondary endpoints included the proportions of patients achieving ≥ 75% and ≥ 90% improvement in the Eczema Area and Severity Index (EASI-75 and EASI-90, respectively), ≥ 75% improvement in the SCORing Atopic Dermatitis (SCORAD 75), mean change from baseline in EASI score and proportion of patients achieving a 4-point improvement in the Itch Numeric Rating scale (NRS) for patients aged ≥ 10 years. Primary and key secondary efficacy analyses were conducted on the intent-to-treat population and adjusted for multiplicity. Safety analyses included all randomized patients who received ≥ 1 dose of study treatment. RESULTS: A total of 483 patients were randomized (mean age 12 years). The baricitinib 4 mg equivalent achieved a statistically significant (P < 0.05) improvement vs. placebo on all 16-week endpoints (vIGA 0/1 with ≥ 2-point improvement, EASI-75, EASI-90, SCORAD 75, mean change in EASI score and Itch NRS 4-point improvement for patients aged ≥ 10 years). Improvement (P < 0.05, non-multiplicity adjusted) was also observed for baricitinib 4 mg equivalent vs. placebo in the ability to fall asleep and in reduction of topical corticosteroid use. Few patients discontinued due to adverse events (1.6% for placebo and 0.6% for those treated with baricitinib). There were no deaths, venous thromboembolic events, arterial thrombotic events, major adverse cardiovascular events, malignancies, gastrointestinal perforations or opportunistic infections seen. CONCLUSIONS: The results indicate that baricitinib offers a potential therapeutic option with a favourable benefit-risk profile for paediatric patients with moderate-to-severe AD who are candidates for systemic therapies.

Pimecrolimus for the Treatment of Atopic Dermatitis in Infants: An Asian Perspective.

Atopic dermatitis (AD) is a common chronic, multisystem inflammatory skin disease in pediatric patients. There has been an increase in the incidence of AD in the pediatric population of the Asia-Pacific region. Studies have shown that genetic, epigenetic, environmental and cultural factors may lead to differences in the clinical manifestation and prevalence of AD between races. Early treatment of AD is necessary to prevent the atopic march leading to comorbidities such as asthma and allergic rhinitis. Topical corticosteroids (TCS) are used as first-line therapy for the treatment of AD, but their long-term usage poses a risk to the patient's health. Pimecrolimus (1%) is a topical calcineurin inhibitor (TCI) that is indicated for the treatment of mild to moderate AD. Pimecrolimus has no apparent increase in adverse events compared to TCS, and it causes less of a burning sensation than tacrolimus. The safety and efficacy of pimecrolimus has been established through various clinical trials; yet, in many Asian countries, the use of pimecrolimus in infants is still restricted due to safety concerns. Based on the available evidence, the expert panel recommends pimecrolimus in infants between 3 months and 2 years of age in the Asian population.

Long-Term Use of Antiperspirant is Associated with a Low Risk of Postoperative Complications in Patients with Axillary Osmidrosis.

Purpose: Many patients with axillary osmidrosis (AO) cannot tolerate the local irritation of strong antiperspirants and discontinue AO use within a short time. This study evaluates the effect of long-term antiperspirant use on postoperative complications after osmidrosis surgery. Patients and Methods: A total of 116 females (66 antiperspirant and 50 non-antiperspirant cases) who underwent osmidrosis surgery were retrospectively reviewed. Postoperative complications were compared between the 2 groups. Results: Patients with long-term antiperspirant use had a lower risk of full-thickness skin necrosis compared with those who did not use antiperspirants (odds ratio [OR] = 0.048, 95% confidence Interval [CI]: 0.006-0.392, p = 0.005). Patients with antiperspirants use also had a lower risk of moderate-to-severe erythema compared to those without antiperspirants use (moderate vs mild erythema: OR = 0.351, 95% CI: 0.129-0.959, p = 0.041; severe vs mild erythema: OR = 0.161, 95% CI: 0.047-0.550, p = 0.004). Patients who used antiperspirants also had a lower risk of severe skin erosion compared to those who did not use antiperspirants (severe vs mild skin erosion: OR = 0.164, 95% CI: 0.037-0.725, p = 0.017). There was a trend of lower risk in moderate skin erosion in patients with antiperspirant use compared to those without antiperspirant use, but it was not statistically significant (moderate vs mild epidermal damage and peeling: OR = 0.406, 95% CI: 0.158-1.043, p = 0.061). Conclusion: Postoperative complications in patients with AO who undergo osmidrosis surgery are lower in those with a long-term antiperspirant use compared to patients who did not use antiperspirants.

Efficacy of Dupilumab on Different Phenotypes of Adult with Moderate-to-Severe Atopic Dermatitis in Taiwan: A Real-World Study.

To determine phenotype-related dupilumab response in adult patients with atopic dermatitis (AD), this multicenter, retrospective study included 111 adults with moderate-to-severe AD in Taiwan, with median age of 31.5 years (18-87) and 71 (64.0%) males. Patients received dupilumab 300 mg per two to three weeks up to 12 months. We found a significant improvement after 4 and 16 weeks of treatment in all patients for all the assessed scores, including eczema area and severity index (EASI) improvement ≥50% (EASI-50) and 75% (EASI-75), EASI reaching minimal clinically important difference (MCID), and Investigator's Global Assessment (IGA) improvement ≥2. Importantly, prior to asthma, early AD onset and 3-week drug intervals were significantly associated with a high proportion of EASI-75 at month 12, while prurigo and lichenoid phenotypes were associated with a lower proportion of EASI-75 at month 12. However, the majority of adverse events were mild in severity. In conclusion, our study results identify phenotype-related dupilumab response at month 12 in adults with moderate-to-severe AD, and we suggest that treatment should not be discontinued until reaching a satisfactory clinical response.

Buschke-Ollendorff syndrome presenting with asymptomatic yellowish papules and leg length discrepancy: A case report.

Buschke-Ollendorff syndrome (BOS) is a rare, usually benign, autosomal dominant genetic disease affecting about 0.005% globally. BOS commonly manifests with asymptomatic connective tissue nevi, sometimes with sclerotic bone lesions like osteopoikilosis or melorheostosis. However, BOS may develop severe, symptomatic complications that require surgical intervention. Here we report a 9-year-8-month girl presenting with multiple nonpruritic, nonpainful skin plaques scattered around the trunk, buttocks, and bilateral legs. She had a history of right varus foot with inadequate plantar flexion. Upon visiting, obvious leg length discrepancy (LLD) was noted. Lesional biopsy revealed increased fibroblasts within dermal collagen bundles. Verhoeff-van Gieson stain revealed scattered foci of thickened elastic fibers between collagen fibers, especially in the mid-dermis. Radiographic examination of the lower extremities showed multiple small, round-to-oval shaped, radiopaque spots on the pelvic bones, femurs, tibiae, and both feet. Hyperostosis along the long axis with "dripping candle wax" appearance was characteristic of osteopoikilosis and melorheostosis. Genetic analysis showed heterozygous point mutation in exon 1 of LEMD3 gene (c.1323C>A, p.Y441X), confirming diagnosis of BOS. Sequential and epiphyseodesis were performed to correct LLD with a favorable outcome at 2-year follow-up. BOS associated with severe bone abnormalities is rare, but orthopedic surgical intervention can provide satisfactory outcome.

Clinical features and outcomes in children with Stevens-Johnson syndrome and toxic epidermal necrolysis.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening cutaneous conditions. However, studies of pediatric SJS/TEN are limited. To investigate the causes, clinical course, outcomes and complications of SJS and TEN in children. This retrospective study included 47 pediatric patients (aged < 18 years) with SJS, SJS/TEN, or TEN treated at Chang Gung Memorial Hospital, Taiwan, between January 2009 and December 2019. ALDEN scores and serological tests were used to assess causes and SCORTEN scores were applied to evaluate disease severity. Forty-seven patients, including 30 with SJS, 6 with SJS/TEN, and 11 with TEN were included. Median age was 8 years (range 1-17 years); 51.1% were male. Thirty-three cases (70.2%) were caused by drugs and infectious pathogens were suspected in 14 cases (29.8%). Oxcarbazepine (5/47, 10.6%) and amoxicillin (5/47, 10.6%) were the most often-implicated drugs, and Mycoplasma infection (9/47, 19.1%) was the predominant infectious cause. Only one TENS patient died (mortality rate 1/47, 2.1%) due to septic shock with ARDS, acute renal failure and cardiopulmonary shock. Median hospital stay was 15.5 (3-42) days. Pulmonary involvement (2/39, 5.1%), including pneumonia and ARDS, was noted in acute stage. Long-term sequelae were ocular involvement (6/39, 15.4%), nail dystrophy (4/39, 10.3%) and post-inflammatory hypo-/hyperpigmentation (3/39, 7.7%). In the present study, pediatric patients with SJS, SJS/TEN, or TEN have good outcomes with few long-term complications and low mortality. Mycoplasma is the most common infectious cause in pediatric SJS/TEN. Ocular discomfort, nail dystrophy and skin dyschromia are common long-term sequelae requiring regular follow-up.

Amplified spontaneous emission from all-inorganic perovskite on a flexible substrate with silk fibroin.

Stretchable microcavity lasers reveal potential application in flexible displays, biomedicine, and wearable devices in the near future. In this work, we investigated the characteristic of amplified spontaneous emission (ASE) from all inorganic CsPbBr3 QDs on a flexible PET substrate with the assistance of biocompatible silk fibroin (SF) film. In comparison with the sample on PET directly, the ASE of all-inorganic perovskite film revealed a lower threshold of 32.7 µJ/cm2, higher slope efficiency, and a larger gain coefficient of around 100.0 cm-1 owing to the better stack and good arrangement of the CsPbBr3 QDs on top of the SF film. For the temperature-dependent ASE measurement, the larger characteristic temperature of around 277 K is obtained from CsPbBr3 QD/SF film, and the emission peak reveals a slight shift with temperature variation, which indicates its temperature-insensitive property. As the curvature of flexible substrate increases under the mechanical bending, the lasing threshold of CsPbBr3 QD/SF film was reduced along with the increase in slope efficiency owing to the enhancement in the index guiding effect.

High-Density Horizontal Stacking of Chondrocytes via the Synergy of Biocompatible Magnetic Gelatin Nanocarriers and Internal Magnetic Navigation for Enhancing Cartilage Repair.

Osteoarthritis (OA) is a globally occurring articular cartilage degeneration disease that adversely affects both the physical and mental well-being of the patient, including limited mobility. One major pathological characteristic of OA is primarily related to articular cartilage defects resulting from abrasion and catabolic and proinflammatory mediators in OA joints. Although cell therapy has hitherto been regarded as a promising treatment for OA, the therapeutic effects did not meet expectations due to the outflow of implanted cells. Here, we aimed to explore the repair effect of magnetized chondrocytes using magnetic amphiphilic-gelatin nanocarrier (MAGNC) to enhance cellular anchored efficiency and cellular magnetic guidance (MG) toward the superficial zone of damaged cartilage. The results of in vitro experiments showed that magnetized chondrocytes could be rapidly guided along the magnetic force line to form cellular amassment. Furthermore, the Arg-Gly-Asp (RGD) motif of gelatin in MAGNC could integrate the interaction among cells to form cellular stacking. In addition, MAGNCs upregulated the gene expression of collagen II (Col II), aggrecan, and downregulated that of collagen I (Col I) to reduce cell dedifferentiation. In animal models, the magnetized chondrocytes can be guided into the superficial zone with the interaction between the internal magnetic field and MAGNC to form cellular stacking. In vivo results showed that the intensity of N-sulfated-glycosaminoglycans (sGAG) and Col II in the group of magnetized cells with magnetic guiding was higher than that in the other groups. Furthermore, smooth closure of OA cartilage defects was observed in the superficial zone after 8 weeks of implantation. The study revealed the significant potential of MAGNC in promoting the high-density stacking of chondrocytes into the cartilage surface and retaining the biological functions of implanted chondrocytes for OA cartilage repair.

Kimura Disease of the Thigh Treated With Surgical Excision and Dupilumab.

ABSTRACT: Kimura disease (KD) is a rare, chronic inflammatory disorder presenting with solitary or multiple masses. Treatment options include surgical excision, corticosteroids, and radiotherapy; however, optimal therapy remains to be established. Moreover, efficacy of a humanized monoclonal antibody, dupilumab (Dupixent), requires to be demonstrated. Here, we present a 36-year-old male patient with an enlarging mass in the left medial thigh and chronic eczema over the abdomen and lower legs. Kimura disease was diagnosed after surgical excision. Postoperative treatment with dupilumab was applied with an initial dose of 600 mg followed by 300 mg every 2 weeks for 8 months. No recurrence of KD was observed in the 1-year follow-up. The eczematous lesions improved greatly. To our knowledge, this is the first report of using dupilumab for treating KD.

Efficacy and safety of picosecond 755-nm alexandrite laser for treatment of nevus of Ota in Taiwanese children: A retrospective study.

OBJECTIVES: To evaluate the efficacy and safety of picosecond 755-nm alexandrite laser in the treatment of nevus of Ota in children. MATERIALS AND METHODS: A retrospective study was conducted by reviewing medical charts and photographs of 86 Taiwanese children with various types of nevus of Ota between January 2017 and September 2020. Picosecond 755-nm alexandrite laser therapy was used to treat pigmentary lesions. Percent clearance of lesions during treatment and the treatment time required to achieve 95%-100% clearance were determined. RESULTS: According to Tanino's classification or Peking University Medical College Hospital (PUMCH) classification of nevus of Ota, most patients belonged to Tanino's Type II (32%) and Type III (38%) or PUMCH Type IIb (33%) and Type IIIb (26%), which indicated that the nevus was mainly distributed in the forehead, upper and lower eyelid, zygomatic, cheek, and temple regions. After treatment with picosecond 755-nm alexandrite laser, 96.5% of the patients achieved 95%-100% clearance with an average of 4.3 treatment sessions. The earlier onset of lesions (before 5 months of age) and the darker Fitzpatrick skin types (type IV vs. type III) significantly increased the number of treatments required to achieve clear response, while sex, age at first treatment, Tanino's classification of nevus, and color of nevus had no significant effect. Posttreatment hypopigmentation or hyperpigmentation was transient and resolved within 6 months. No serious response of the skin was evident. CONCLUSION: Picosecond 755-nm alexandrite laser treatment of nevus of Ota in children was safe and effective. The treatment was well-tolerated, and only a few transient, minor side effects occurred.

Taiwanese Dermatological Association consensus for the management of atopic dermatitis: A 2020 update.

BACKGROUND/PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory disease commonly seen in children and increasingly recognized in adults. With recent advances in the therapeutic development for AD, the Taiwanese Dermatological Association (TDA) established a committee to update the consensus for AD management in Taiwan. This report describes the 2020 updated consensus for the management of AD. METHODS: A panel of 11 core members was convened to review and discuss aspects of AD management and draft recommendation during the first two meetings. The 2015 TDA consensus and the 2017 European guideline, along with recent peer-reviewed articles, serve as the foundation for the update. In the third meeting, AD expert dermatologists selected on a national scale were invited to vote on the final statements. A total of 27 dermatologists attended the final meeting. The consensus was achieved when ratings of 7-9 (out of a total score of 9) accounted for ≥ 75% of the total votes. RESULTS: Consensus was achieved on the therapeutic options for AD by lines of treatment. A treatment algorithm was presented to illustrate the place of each modality in terms of basic care, acute disease control, and maintenance therapy. Special considerations for the pediatric population, as well as for women during pregnancy and lactation, are discussed. CONCLUSION: Topical corticosteroids with long-term emollient-based therapies remain the cornerstone of AD treatment. Systemic treatments are indicated when topical therapies and phototherapy fail to control the disease. The recent approval of dupilumab and emerging targeted therapies are expected to bring significant clinical benefit for patients whose disease is inadequately managed by existing options.

Clinical and epidemiological characteristics of tinea capitis in northern Taiwan during 2014-2019: An unusual bimodal distribution of patients and comparison of paediatric and adult cases.

Tinea capitis (TC) mainly occurs in children, and related studies in adults are rare. We aimed to investigate the current epidemiological, clinical and mycological characteristics of TC and to compare adult and paediatric patients in northern Taiwan. We conducted a retrospective study at Chang Gung Memorial Hospital, Linkou Branch, from 2014 to 2019. The dataset included age, sex, records of underlying diseases, animal contact history, frequent hair salon visits, clinical patterns, treatment and outcome via chart or phone call reviews. The average ages of 72 children and 104 adults recruited were 6.0 and 74.0 years, respectively. A female predominance was noted in both groups, and the ratio of females was significantly higher in adults (94.2% vs 59.7%, P < .0001). Microsporum canis (76.4%) and Trichophyton mentagrophytes (11.1%) in children, and M. canis (49.0%) and T. violaceum (31.7%) in adults were the most common pathogens. Adults were more likely to be infected with T. violaceum (OR = 10.14, 95% CI = 2.04-50.26) than children. In contrast, adults were less likely to be infected with M. canis than children (OR = 0.31, 95% CI = 0.11-0.90). Furthermore, adults visited hair salons more, had less animal contact and were more immunosuppressed than children. TC is not unusual in the adult population. Dermatologists are advised to realise risk factors such as immunosuppression and regular hair salon visit in adult TC.

Noise-like pulse generation around 1.3-µm based on cascaded Raman scattering.

Based on cascaded Raman scattering, near-infrared (NIR) noise-like pulses (NLPs) were successfully demonstrated using a Yb-doped fiber amplifier system. Through a nonlinear fiber amplifier using a germanium-zirconia-silica Yb3+-doped single mode fiber as a gain fiber, the fourth-order Stokes wave (4th-SW) can be excited to extend the emission peak of approximately 1.2-µm and a 3-dB bandwidth of approximately 130 nm. To further shift the wavelength more efficiently toward 1.3 µm, filtered NLPs with an emission peak at 1075 nm were adopted as seeded pulses to excite the fifth-order Stokes wave (5th-SW) because of the better conversion efficiency of stimulated Raman scattering without gain competition with Yb-doped fiber. The generated NIR NLPs were shown to be an excellent light source for the photoluminescence emission from three photon absorption of perovskite to illustrate the red shift of the emission peak owing to the reabsorption effect.

Efficacy and safety of indigo naturalis ointment in Treating Atopic Dermatitis: A randomized clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Indigo naturalis, a herbal medicine with a history of use dating back to ancient times, may be a good alternative topical treatment for atopic dermatitis (AD). AIM OF THE STUDY: To provide empirical evidence of the efficacy and safety of Indigo naturalis ointment in treating AD. MATERIALS AND METHODS: In this randomized double-blind clinical trial, participants aged 6 to 65 years with AD affecting less than 40% of their body surface area (BSA) and an Investigator's Global Assessment (IGA) score of 2 to 4 were randomized (2:1) to receive either Lindioil ointment or a vehicle ointment twice daily for 6 weeks. The primary endpoint was the percentage change in the Eczema Area Severity Index (EASI) from baseline to week 6. Secondary endpoints were as follows: EASI improvement ≥50%, 75%, and 90%; IGA score; BSA affected by AD; pruritus severity; and Dermatology Life Quality Index. The safety assessment included adverse events (AEs), laboratory tests, and physical examinations. RESULTS: The Lindioil group (32 participants) and vehicle group (16 participants) achieved mean percentage EASI reductions of 49.9% ± 36.5% (95% CI 36.8%-63.1%) and 19.6% ± 52.2% (95% CI -8.2%-47.4%), respectively (P = 0.0235). The Lindioil group also showed greater improvement in every secondary assessment category. No significant AEs occurred. CONCLUSION: Indigo naturalis ointment is effective for treating mild to severe AD topically, and appears to be safe. This is the first clinical trial to provide evidence supporting topical indigo-based AD treatment. ClinicalTrials.gov identifier: NCT02669888.

Cutaneous involvement of polymorphic post-transplant lymphoproliferative disorder in a child after liver transplantation.

Post-transplantation lymphoproliferative disorder (PTLD) is one of the most common de novo malignancies in patients who receive immunosuppressive therapy after solid organ transplantation. We report a case of a 5-year-old girl who presented with indurated violaceous skin nodules 3.5 years post-liver transplantation, diagnosed as polymorphic PTLD, also involving Waldeyer's ring, spleen, and multiple lymph nodes. Through reduction of immunosuppression, most of the lesions resolved and the liver allograft was preserved.

A Randomized, Double-Blind, Placebo-Controlled Trial Assessing the Oral Administration of a Heat-Treated Lactobacillus paracasei  Supplement in Infants with Atopic Dermatitis Receiving Topical Corticosteroid Therapy.

BACKGROUND/AIMS: Atopic dermatitis (AD) is a common disease in infancy, for which topical steroids are the first-line therapy but have side effects. Innovative approaches are needed to reduce the burden of AD and corticosteroid usage in infants. METHODS: The once-daily consumption of heat-treated probiotic Lactobacillus paracasei GM-080 or placebo for 16 weeks as supplementary approach to topical treatment with fluticasone propionate cream was compared in AD infants aged 4-30 months. Outcomes were SCORAD and its subscores, TEWL, Infants' Dermatitis Quality of Life Index (IDQOL), corticoid "sparing effect," CCL17/TARC, and IgE status. RESULTS: SCORAD, objective SCORAD, itching, and IDQOL decreased significantly (p < 0.001) over the treatment period in both treatment groups. Slight decreases (ns) were noted in TEWL in lesional and unaffected skin and CCL17 levels. There were no differences between the treatment groups. Total IgE increased over the treatment period in both groups, with significantly higher increase in the heat-treated probiotic group (p = 0.038). There was no evidence of a corticoid "sparing effect" by the probiotic. CONCLUSIONS: In this design, the probiotic L. paracasei was not beneficial as a complementary approach to topical corticosteroids in infants with AD. However, slight beneficial effects may have been masked by the moderate potency corticoid.

The Medication Risk of Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis in Asians: The Major Drug Causality and Comparison With the US FDA Label.

Specific ethnic genetic backgrounds are associated with the risk of Stevens-Johnson syndrome / toxic epidermal necrolysis (SJS/TEN) especially in Asians. However, there have been no large cohort, multiple-country epidemiological studies of medication risk related to SJS/TEN in Asian populations. Thus, we analyzed the registration databases from multiple Asian countries who were treated during 1998-2017. A total 1,028 SJS/TEN cases were identified with the algorithm of drug causality for epidermal necrolysis. Furthermore, those medications labeled by the US Food and Drug Administration (FDA) as carrying a risk of SJS/TEN were also compared with the common causes of SJS/TEN in Asian countries. Oxcarbazepine, sulfasalazine, COX-II inhibitors, and strontium ranelate were identified as new potential causes. In addition to sulfa drugs and beta-lactam antibiotics, quinolones were also a common cause. Only one acetaminophen-induced SJS was identified, while several medications (e.g., oseltamivir, terbinafine, isotretinoin, and sorafenib) labeled as carrying a risk of SJS/TEN by the FDA were not found to have caused any of the cases in the Asian countries investigated in this study.

Randomized, controlled trial of TNF-α antagonist in CTL-mediated severe cutaneous adverse reactions.

BACKGROUND: Cytotoxic T lymphocyte-mediated (CTL-mediated) severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), are rare but life-threatening adverse reactions commonly induced by drugs. Although high levels of CTL-associated cytokines, chemokines, or cytotoxic proteins, including TNF-α and granulysin, were observed in SJS-TEN patients in recent studies, the optimal treatment for these diseases remains controversial. We aimed to evaluate the efficacy, safety, and therapeutic mechanism of a TNF-α antagonist in CTL-mediated SCARs. METHODS: We enrolled 96 patients with SJS-TEN in a randomized trial to compare the effects of the TNF-α antagonist etanercept versus traditional corticosteroids. RESULTS: Etanercept improved clinical outcomes in patients with SJS-TEN. Etanercept decreased the SCORTEN-based predicted mortality rate (predicted and observed rates, 17.7% and 8.3%, respectively). Compared with corticosteroids, etanercept further reduced the skin-healing time in moderate-to-severe SJS-TEN patients (median time for skin healing was 14 and 19 days for etanercept and corticosteroids, respectively; P = 0.010), with a lower incidence of gastrointestinal hemorrhage in all SJS-TEN patients (2.6% for etanercept and 18.2% for corticosteroids; P = 0.03). In the therapeutic mechanism study, etanercept decreased the TNF-α and granulysin secretions in blister fluids and plasma (45.7%-62.5% decrease after treatment; all P < 0.05) and increased the Treg population (2-fold percentage increase after treatment; P = 0.002), which was related to mortality in severe SJS-TEN. CONCLUSIONS: The anti-TNF-α biologic agent etanercept serves as an effective alternative for the treatment of CTL-mediated SCARs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01276314. FUNDING: Ministry of Science and Technology of Taiwan.

Characteristics of noise-like pulse with broad bandwidth based on cascaded Raman scattering.

A noise-like pulse (NLP) with broadband emission spectrum and superior beam quality from a dispersion managed mode-locked Yb-doped fiber laser has been demonstrated based on stimulated Raman scattering. After insertion of a 150 m long single mode fiber into the laser cavity, the second order stoke wave from 1.3 MHz repetition rate of NLP can be excited. With a 320 mW pump power, the highest pulse energy of NLP was about 35.1 nJ and the emission spectrum was extended from 1000 to 1160 nm. Through a multi-mode fiber laser, the broad bandwidth NLP can produce relatively low speckle noise imaging with contrast below 0.04. The generated NLPs can be used as a superior light source for the biomedical diagnosis and laser projection in the near future.