Facial erythema in patients with atopic dermatitis treated with Dupilumab - a descriptive study of morphology and Aetiology.

BACKGROUND: The development of dermatitis on face and neck, which was not described in phase 3 clinical trials, has been reported in the literature in patients treated with dupilumab. Little is known regarding the causes or defining features of the facial dermatitis. OBJECTIVES: We conducted surveys of consecutive patients with AD on dupilumab to describe its clinical features, morphology and aetiology. METHODS: A multi-centre prospective cohort study was conducted from 1 January 2020, to 31 December 31 2020. A total of 162 patients under dupilumab treatment were asked to complete a questionnaire and patients were evaluated by dermatologists. RESULTS: Of all 162 patients, 137 (84.6%) patients reported pre-existing facial dermatitis prior to dupilumab therapy. One hundred and twenty-one (88.3%) patients with pre-existing facial dermatitis reported improvement of their facial dermatitis with dupilumab therapy, nine (6.6%) patients reported no change after the treatment and seven (4.3%) patients of them got worse after the treatment (exacerbation group). Of 25 patients who reported no pre-existing active facial dermatitis, six (24%) patients reported new-onset facial erythema after the starting dupilumab therapy (new-onset group). A large proportion of the patients in both the exacerbation (86%) and new-onset groups (67%) had a history of facial TCS use. Both groups showed similar clinical manifestations and distribution with few differences. CONCLUSIONS: The vast majority of patients treated with dupilumab in academic institutions from Korea and the United States experienced improvement in their facial dermatitis with dupilumab therapy. A small proportion of patients had new onset and exacerbation. Although the mechanisms of this adverse event remain unclear, steroid withdrawal should be considered as a diagnosis of the erythema in some patients.

Pandemic influenza virus, pH1N1, induces asthmatic symptoms via activation of innate lymphoid cells.

BACKGROUND: The pandemic strain of the influenza A virus (pH1N1) in 2009 caused many complications in patients. In this study, we introduce asthmatic symptoms as a complication of pH1N1 infection in children, not having a relationship with asthma history. The aim of this study was to quantify asthmatic symptoms in pH1N1-infected children and elucidate the underlying mechanisms of airway hyper-responsiveness (AHR) induced in a murine model of pH1N1 infection. METHODS: As a retrospective study, pH1N1-infected children who were hospitalized with moderate to severe acute asthmatic symptoms were enrolled and administered a methacholine challenge test (MCT) at 3 months post-discharge. Additionally, the induction of AHR by pH1N1 infection was measured by MCT in wild-type and Rag1(-/-) mice. The effect of the innate immune response on the development of AHR following pH1N1 infection was investigated. RESULTS: More than 70% of the pH1N1-infected children without a pre-infection diagnosis of asthma had a negative response on the MCT. None of these children had recurrent wheezing or asthma during the 3 years following pH1N1 infection. The development of AHR in pH1N1-infected mice was associated with an elevation in IL-33 and innate lymphoid cells 2 (ILC2). CONCLUSIONS: This study demonstrates that pH1N1 infection directly induces transient asthmatic symptoms in patients regardless of their medical history. pH1N1 infection was shown to stimulate the rapid development of AHR and Th2-type cytokine secretion in mice via the activation of ILC2; it may be activated independently of adaptive immunity.

BLZ8 activates a plastidial peroxiredoxin and a ferredoxin to protect Chlamydomonas reinhardtii against oxidative stress.

Reactive oxygen species (ROS) cause damage to various cellular processes in almost all organisms, in particular photosynthetic organisms that depend on the electron transfer chain for CO2 fixation. However, the detoxifying process to mitigate ROS damage has not been studied intensively in microalgae. Here, we characterized the ROS detoxifying role of a bZIP transcription factor, BLZ8, in Chlamydomonas reinhardtii. To identify downstream targets of BLZ8, we carried out comparative genome-wide transcriptomic profiling of BLZ8 OX and its parental CC-4533 under oxidative stress conditions. Luciferase reporter activity assays and RT-qPCR were performed to test whether BLZ8 regulates downstream genes. We performed an in silico functional gene network analysis and an in vivo immunoprecipitation assay to identify the interaction between downstream targets of BLZ8. Comparative transcriptomic analysis and RT-qPCR revealed that overexpression of BLZ8 increased the expression levels of plastid peroxiredoxin1 (PRX1) and ferredoxin-5 (FDX5) under oxidative stress conditions. BLZ8 alone could activate the transcriptional activity of FDX5 and required bZIP2 to activate transcriptional activity of PRX1. Functional gene network analysis using FDX5 and PRX1 orthologs in A. thaliana suggested that these two genes were functionally associated. Indeed, our immunoprecipitation assay revealed the physical interaction between PRX1 and FDX5. Furthermore, the complemented strain, fdx5 (FDX5), recovered growth retardation of the fdx5 mutant under oxidative stress conditions, indicating that FDX5 contributes to oxidative stress tolerance. These results suggest that BLZ8 activates PRX1 and FDX5 expression, resulting in the detoxification of ROS to confer oxidative stress tolerance in microalgae.

Regulation of immune responses to Strongyloides venezuelensis challenge after primary infection with different larvae doses.

Nematode infections are generally followed by high rates of reinfection, leading to elevated prevalence in endemic areas. Therefore, the effective control of nematode infections depends on understanding the induction and regulation of protective mechanisms. However, most experimental models for protective immune response against nematodes use high parasite exposure, not always reflecting what occurs naturally in human populations. In this study, we tested whether infecting mice with different Strongyloides venezuelensis larvae loads would affect protective responses against reinfection. Interestingly, we found that a previous infection with 10-500 larvae conferred high rate of protection against reinfection with S. venezuelensis in mice, by destroying large numbers of migrating larvae. However, low-dose priming did not abolish adult worm maturation, as detected in high-dose primed group. Results also indicated that a previous low-dose infection delayed the development of cellular infiltrate, while a high inoculum rapidly induced these inflammatory features. Cytokine production by splenocyte cultures of challenge infected mice demonstrated that low-dose priming had increased production of IL-4 and IFN-gamma, while high-dose induced IL-4 production but not IFN-gamma. Our data support the hypothesis that low-dose nematode infection does not induce a polarized type-2 immune response, allowing adult worm survival.

Different clinical and magnetic resonance imaging features between Charcot-Marie-Tooth disease type 1A and 2A.

Charcot-Marie-Tooth disease type 1A (CMT1A) is the more frequent cause of demyelinating CMT, and CMT2A is the most common cause of axonal CMT. We conducted a magnetic resonance imaging (MRI) study on 39 CMT1A and 21 CMT2A patients to compare their neuroimaging patterns and correlate with clinical features. CMT1A patients showed selective fatty infiltration with a preference for anterior and lateral compartment muscles, whereas CMT2A patients showed a preference for superficial posterior compartment muscles. Early-onset CMT2A patients showed more severe leg fatty atrophy than late-onset CMT2A patients. In late-onset CMT2A, soleus muscle was the earliest, and most severely affected than the other leg muscles. Selective involvement of intrinsic foot muscles is a characteristic pattern of minimal CMT1A and CMT2A. Our MRI study demonstrates different patterns of fatty infiltration involving superficial posterior compartment muscles in CMT2A (partial T-type), and peroneal nerve innervated muscles in CMT1A (P-type).

Surgical outcomes of tympanoplasty using a sterile acellular dermal allograft: a prospective randomised controlled study.

Acellular human dermal allografts have been shown to be effective for soft-tissue implantation. We compared treatment outcomes of tympanoplasty using tragal perichondrium and acellular human dermal allograft (MegaDerm®). In a prospective randomised controlled study, 60 patients scheduled to undergo tympanoplasty were randomly assigned to the autologous tragal perichondrium group (n = 33) or acellular human dermal allograft group (n = 27). Postoperative hearing gain, graft success rate at 1 and 6 months and operation times were compared between groups. Graft success rate, defined as the complete closure of tympanic membrane perforation, did not show any significant intergroup difference (75.8% vs 85.2%, p = 0.519). Air conduction thresholds and air-bone gaps showed significant improvements in both groups; from 38.7 ± 15.9 dB to 30.2 ± 15.6 dB (p < 0.001) and from 17.8 ± 7.3 dB to 11.5 ± 7.0 (p = 0.001) in the autologous tragal perichondrium group, and from 30.4 ± 12.2 dB to 24.5 ± 13.0 dB (p = 0.006) and from 14.3 ± 5.1 dB to 7.6 ± 4.6 dB (p < 0.001) in the acellular human dermal allograft group. The amount of hearing gain (p = 0.31) and closure of air-bone gap (p = 0.863) were not meaningfully different between groups. The mean operation time was significantly lower in the acellular human dermal allograft group (35.2 min vs 27.4 min, p = 0.039). In this prospective randomised controlled study, acellular human dermal allograft was shown to be an effective alternative to tragal perichondrium, with similar graft success rates and postoperative hearing results, but with reduced operation times.

Rectus femoris muscle atrophy and recovery caused by preoperative pretibial traction in femoral shaft fractures-comparison between traction period.

BACKGROUND: Skeletal traction is performed to temporarily stabilize fracture sites before surgery in patients with femoral fracture. To date, however, there is no study evaluating the difference in the degree of the recovery, of the muscle strength, as well as muscle atrophy following skeletal traction. The purpose of this study was to compare the degree of recovery of rectus femoris muscle strength after surgery in association with muscle atrophy by analyzing the duration of preoperative tibial traction, age and sex in patients with femoral fracture. HYPOTHESIS: Rectus femoris muscle atrophy will progress depending on the duration of preoperative tibial traction, age and sex in patients with femoral fracture. PATIENTS AND METHOD: Thirty-one patients who underwent preoperative pretibial skeletal traction and intramedullary nailing were divided into two groups according to the traction period: group A (n=12) with a duration of traction of <7 days (mean: 4.08±1.78 days) and group B (n=19) ≥7 days (mean: 13.63±7.17 days). The degree of muscle atrophy and recovery were compared between the two groups, according to age and gender. The degree of muscle atrophy was measured by the difference in thickness of the rectus femoris between pre- and post-traction using ultrasound. The degree of muscle recovery was evaluated by the Q-setting and heel off time. Clinical outcome was evaluated by the non-union rate and Lysholm score. RESULTS: The degree of muscle atrophy was 0.99±0.14mm in group A and 2.22±0.11mm in group B (P<0.001). The Q-setting time was 4.83±0.94 days in group A and 6.56±1.38 days in group B (P=0.001). Heel off time was also shorter in group A at 2.58±0.90 days, taking 3.72±1.27 days in group B (P=0.012). The recovery rate in the rectus femoris was significantly higher in group A than in group B (P<0.001). There was no significant difference in non-union rate between group A and B (P=0.672) but the mean Lysholm score at the last follow-up was significantly higher in group A than in group B (P=0.006). However, no significant differences were detected in the mean thickness of the rectus femoris, Q-setting, and heel off time between the different age and gender groups (P<0.05). CONCLUSIONS: The prolonged duration of preoperative skeletal traction indicates not only that the resulting disuse atrophy would progress further but also that the muscle atrophy would be accelerated more rapidly for shorter periods of time, based on a cut-off value of 7 days. In addition, the rate of rectus femoris muscle recovery and clinical outcomes were lower in patients undergoing traction for longer periods of time. This indicates that it would be effective for increasing the rate of the recovery and minimizing the occurrence of post surgical complications if surgeons could perform surgery at the earliest possible opportunity following traction, within seven days after the onset of trauma. LEVEL OF EVIDENCE: IV, retrospective cohort study.

Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells.

OBJECTIVES: Eukaryotic translation initiation factor 3 (eIF3) is a multi-subunit complex that plays a critical role in translation initiation. Expression levels of eIF3 subunits are elevated or decreased in various cancers, suggesting a role for eIF3 in tumorigenesis. Recent studies have shown that the expression of the eIF3b subunit is elevated in bladder and prostate cancer, and eIF3b silencing inhibited glioblastoma growth and induced cellular apoptosis. In this study, we investigated the role of eIF3b in the survival of osteosarcoma cells. METHODS: To investigate the effect of eIF3b on cell viability and apoptosis in osteosarcoma cells, we first examined the silencing effect of eIF3b in U2OS cells. Cell viability and apoptosis were examined by the Cell Counting Kit-8 (CCK-8) assay and Western blot, respectively. We also performed gene profiling to identify genes affected by eIF3b silencing. Finally, the effect of eIF3b on cell viability and apoptosis was confirmed in multiple osteosarcoma cell lines. RESULTS: eIF3b silencing decreased cell viability and induced apoptosis in U2OS cells, and by using gene profiling we discovered that eIF3b silencing also resulted in the upregulation of tumour necrosis factor receptor superfamily member 21 (TNFRSF21). We found that TNFRSF21 overexpression induced cell death in U2OS cells, and we confirmed that eIF3b silencing completely suppressed cell growth in multiple osteosarcoma cell lines. However, eIF3b silencing failed to suppress cell growth completely in normal fibroblast cells. CONCLUSION: Our data led us to conclude that eIF3b may be required for osteosarcoma cell proliferation by regulating TNFRSF21 expression.Cite this article: Y. J. Choi, Y. S. Lee, H. W. Lee, D. M. Shim, S. W. Seo. Silencing of translation initiation factor eIF3b promotes apoptosis in osteosarcoma cells. Bone Joint Res 2017;6:186-193. DOI: 10.1302/2046-3758.63.BJR-2016-0151.R2.

Follow-up of coil occlusion of patent ductus arteriosus.

OBJECTIVE: We sought to determine the prevalence and fate of residual ductal shunting following coil occlusion of patent ductus arteriosus. BACKGROUND: Although transcatheter coil occlusion of patent ductus arteriosus has gained popularity, few follow-up data have been reported. METHODS: A review of 75 patients who underwent coil occlusion was performed. Residual shunting was investigated by Doppler echocardiography in follow-up. Angiograms were reviewed to obtain minimal ductal diameter and ductal angiographic type. RESULTS: Residual shunts were found in 31 patients (41%) on the day of the procedure, and of these, spontaneous closure was noted in 17 (55%) at 2 weeks to 20 months of follow-up. Of the 75 patients studied, 5 (7%) required a second coil procedure, and 10 (13%) remained with persistent residual shunts at most recent follow-up. Actuarial analysis estimated a 6 +/- 5% prevalence of residual shunts 20 months after a single coil procedure and 3 +/- 3% after all coil procedures. Minimal ductal diameter was associated with immediate complete ductal occlusion by a single coil. These patients had significantly smaller (p = 0.003) minimal ductal diameters (1.2 +/- 0.7 mm) than those who required two coils during their initial procedure to achieve immediate occlusion (1.9 +/- 0.7 mm), those who required a second coil procedure (2.0 +/- 0.9 mm), those who had spontaneous closure of residual shunts (1.9 +/- 0.7 mm) and those with persistent residual shunts (2.0 +/- 0.9 mm). No association was identified between ductal angiographic type and outcome of coil occlusion. No late adverse clinical events of coil occlusion or evidence of recanalization was found. CONCLUSIONS: Small residual shunts are common after coil embolization of patent ductus arteriosus, but most close spontaneously. Actuarial analysis estimates complete closure in 94% at 20 months, and reintervention was required in only 7% of patients.

ECM1 regulates tumor metastasis and CSC-like property through stabilization of ß-catenin.

Extracellular Matrix Protein 1 (ECM1) is a marker for tumorigenesis and is correlated with invasiveness and poor prognosis in various types of cancer. However, the functional role of ECM1 in cancer metastasis is unclear. Here, we detected high ECM1 level in breast cancer patient sera that was associated with recurrence of tumor. The modulation of ECM1 expression affected not only cell migration and invasion, but also sphere-forming ability and drug resistance in breast cancer cell lines. In addition, ECM1 regulated the gene expression associated with the epithelial to mesenchymal transition (EMT) progression and cancer stem cell (CSC) maintenance. Interestingly, ECM1 increased ß-catenin expression at the post-translational level through induction of MUC1, which was physically associated with ß-catenin. Indeed, the association between ß-catenin and the MUC1 cytoplasmic tail was increased by ECM1. Furthermore, forced expression of ß-catenin altered the gene expression that potentiated EMT progression and CSC phenotype maintenance in the cells. These data provide evidence that ECM1 has an important role in cancer metastasis through ß-catenin stabilization.

Usefulness of repeat balloon aortic valvuloplasty in children.

This retrospective study examines all 15 patients who underwent a second balloon dilation procedure for congenital aortic stenosis to determine its safety and efficacy. The recurrent gradient was significantly reduced, but 4 patients had unsatisfactory gradient relief, 3 of whom had previous surgical valvotomies; therefore, we conclude that repeat balloon aortic valvuloplasty is worthwhile, although third balloon dilations may not be beneficial.

Pulmonary artery size and flow disturbances after patent ductus arteriosus coil occlusion.

Transcatheter closure of patent ductus arteriosus with Gianturco coils may impinge on adjacent vascular structures. The left pulmonary artery relative size may decrease after patent ductus arteriosus coil occlusion; thus, serial follow-up echocardiography is recommended to assess long-term left pulmonary artery growth.

Comparison of hospital charges for balloon angioplasty and surgical repair in children with native coarctation of the aorta.

A retrospective review of hospital charges was performed in children > 1 year old with native coarctation of the aorta who underwent balloon angioplasty, primary surgical repair, or elective surgical repair after unsuccessful balloon angioplasty. Hospital charges were less overall in the balloon angioplasty group, although the failure rate was higher.

One-year follow-up of the amplatzer device to close atrial septal defects.

The early and 1-year follow-up of a single United States center using the Amplatzer atrial septal defect closure device is reported. Complete closure was documented in all patients by 1 year after device implantation.

Unique echocardiographic features associated with deployment of the Amplatzer atrial septal defect device.

The purpose of this study was to describe the unique echocardiographic findings associated with deployment of the Amplatzer atrial septal defect (ASD) device. Thirty-five patients (2 to 40 years old; 23 female and 12 male patients) underwent echocardiography during attempted ASD closure with the Amplatzer device. Transesophageal and transthoracic echocardiograms were performed during the placement and follow-up of the device, respectively. In 5 patients, the device was not deployed because of transesophageal echocardiography (TEE) findings (an exceedingly large defect in 3 patients, partial obstruction of the upper right pulmonary vein by the device in 1, and complex atrial septal anatomy in 1). In the remaining 30 patients, after deployment but before release, the device distorted the atrial septum from the normal vertical orientation to an oblique transverse orientation. Excessive septal distortion (i.e., > or =90 degrees in 1 patient) was associated with device embolization upon release. In other patients, TEE also identified mild splaying of the device on the aortic wall, mild abutment of the device upon the mitral valve, and temporary partial obstruction of pulmonary vein flow. Color Doppler revealed residual shunts in 21 of 29 patients immediately after release, but in none of 15 patients at 1-year follow-up. Transesophageal echocardiography is essential to ensure proper Amplatzer device placement. Distortion of the atrial septum and Amplatzer device orientation occur before release but resolve on release from the delivery cable. Small residual shunts are common early, but they resolve in 6 to 12 months.

An unusual case of gastric carcinoma with synchronous non-Hodgkin's lymphoma.

We report a case of synchronous gastric adenocarcinoma and abdominal non-Hodgkin's lymphoma in a 56-year-old man. An explo-laparotomy was performed for the purpose of palliative resection of the stomach and to evaluate the nature of splenic and peri-pancreatic mass lesions. The pathologic stage of the gastric carcinoma was stage IB (T2N0M0) and the clinical stage of the diffuse large cell type lymphoma was IIA2S. Following surgery and chemotherapy, the patient is now in a disease-free state.

Salivary fluoride from fluoride dentifrices or rinses after use of a calcium pre-rinse or calcium dentifrice.

The low concentration of available calcium (Ca) in oral fluids limits the formation of Ca-mediated fluoride deposits that maintain oral fluoride (F) after a topical F treatment. The purpose of this study was to examine if a high concentration of Ca would increase salivary F when used before a F rinse or dentifrice. We found that a Ca pre-rinse (150 mmol/l Ca lactate) or Ca dentifrice (0.084 g Ca glycerolphosphate per gram dentifrice) used immediately before a 60 s 228-ppm F rinse (12 mmol/l NaF) produced a 4.6x or 3.6x increase (p < 0.05) respectively in the 1 h salivary F concentrations over the F rinse alone. Reducing the post-Ca F rinse to 10 s still produced a significant 2.2x increase in salivary F compared to the 60 s F rinse alone. Used with a conventional 1,100 ppm F (i.e. 1,100 microg F per gram) NaF dentifrice (Crest), the above Ca pre-rinse increased 1 h salivary F levels by 2.3x over the F dentifrice alone. However, a F rinse given before a Ca rinse produced no increase in 1 h salivary F concentrations. Although the persistence of these increases requires further study, these results suggest that a moderately high concentration of Ca given shortly before a F rinse or F dentifrice may increase the cariostatic effect of the F product.

Embolization therapy in pediatric cardiology.

Transcatheter embolization therapy has assumed an important role in the management of patients with congenital heart disease. A variety of embolization materials, most commonly steel coils, is available to treat or palliate patients with aortopulmonary collateral vessels or surgical shunts, arteriovenous malformations, and anomalous venovenous connections (common after surgical intervention for the univentricular heart). At many centers, coil occlusion has recently become the treatment of choice for patients with a restrictive patent ductus arteriosus (PDA). This article describes the materials and techniques of embolization therapy, as well as the common indications encountered in the practice of pediatric interventional cardiology.