Summary
Background
Drug reaction with eosinophilia and systemic symptoms (DRESS) is a condition caused by a drug‐induced immune response. Previous reports have found that CXCL10, also known as ...interferon‐γ‐induced protein (IP)‐10, may participate in the pathogenesis of cutaneous adverse drug reactions. However, the exact role of IP‐10 in DRESS and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) has remained unknown.
Objectives
This comparative prospective cohort study aimed to ascertain the roles of the IP‐10/CXCR3 axis in DRESS and SJS/TEN.
Methods
Plasma IP‐10 levels were analysed, and univariate analyses were conducted to assess the relationship between IP‐10, human herpesvirus (HHV)‐6 reactivation and the development of long‐term sequelae. We also performed immunohistochemical staining using skin specimens and flow cytometry to determine the expression of CXCR3 in peripheral blood mononuclear cells (PBMCs).
Results
Significantly higher plasma IP‐10 levels were observed in patients with DRESS with long‐term sequelae (effect size 0·81) and also in those with HHV‐6 reactivation (effect size 0·83). By immunohistochemistry, more abundant IP‐10+ and CXCR3+ cells were demonstrated in the skin lesions of patients with DRESS with HHV‐6 reactivation. The percentages of CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were also higher in the PBMCs of HHV‐6‐reactivated patients with DRESS than in those of patients with SJS/TEN.
Conclusions
Higher plasma IP‐10 levels are associated with the development of long‐term sequelae in DRESS. Higher IP‐10/CXCR3 expression in skin and more abundant CLA+ CXCR3+ CD4+ cells and CLA+ CXCR3+ CD8+ cells were observed in patients with DRESS with HHV‐6 reactivation. The IP‐10/CXCR3 axis is associated with HHV‐6 reactivation and development of long‐term sequelae in DRESS.
What is already known about this topic?
Elevated levels of interferon‐γ‐induced protein‐10 (IP‐10) have been observed in patients with drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).
Patients with DRESS tend to develop long‐term autoimmune sequelae, including type 1 diabetes and autoimmune thyroiditis. IP‐10 has been associated with these autoimmune diseases in previous studies.
What does this study add?
The patients with DRESS with HHV‐6 reactivation exhibited higher levels of IP‐10 in the plasma and skin than the patients with DRESS without HHV‐6 reactivation and the patients with SJS/TEN.
Patients with DRESS with higher plasma IP‐10 levels tended to develop sequelae during long‐term follow‐up.
What is the translational message?
IP‐10 is a useful biomarker to predict the development of long‐term sequelae in patients with DRESS.
Linked Comment: Belloón and Kardaun. Br J Dermatol 2020; 183:804–805.
What is already known about this topic?
Elevated levels of interferon‐γ‐induced protein‐10 (IP‐10) have been observed in patients with drug reaction with eosinophilia and systemic symptoms (DRESS) and Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN).
Patients with DRESS tend to develop long‐term autoimmune sequelae, including type 1 diabetes and autoimmune thyroiditis. IP‐10 has been associated with these autoimmune diseases in previous studies.
What does this study add?
The patients with DRESS with HHV‐6 reactivation exhibited higher levels of IP‐10 in the plasma and skin than the patients with DRESS without HHV‐6 reactivation and the patients with SJS/TEN.
Patients with DRESS with higher plasma IP‐10 levels tended to develop sequelae during long‐term follow‐up.
What is the translational message?
IP‐10 is a useful biomarker to predict the development of long‐term sequelae in patients with DRESS.
Linked Comment: Belloón and Kardaun. Br J Dermatol 2020; 183:804–805.
Plain language summary available online
We studied paediatric patients with human adenovirus (HAdV) infection during the 2011 outbreak in northern Taiwan to define the clinical features of different HAdV genotypes in children.
Between ...January and December 2011, 637 patients <19 years of age exhibited culture-confirmed adenoviral infection in Chang Gung Memorial Hospital, and provided specimens available for genotyping by multiplex real-time PCR. Clinical data were collected retrospectively.
Excluding five cases with multiple genotypes, 632 cases were included for analysis. Three genotypes were identified, including HAdV-3 (429/632; 67.6%), HAdV-7 (144/632; 22.6%) and HAdV-2 (59/632; 9.8%). Median age was 4.58 years (range 2 months to 18 years), with children infected with HAdV-3 significantly older (82.9% >3 years; p <0.001). Of the 621 inpatients, 98.2% had fevers and all exhibited respiratory symptoms, 75 patients (12.1%) had lower respiratory tract infections, 20 (3.2%) required intensive care (HAdV-2: 1; HAdV-3: 8; and HAdV-7: 11), and three died (all HAdV-7-infected). HAdV-3-infected patients were significantly more likely to have upper respiratory symptoms and a high serum C-reactive protein level >100 mg/L, whereas leucocytosis (white blood cell count >15 000/mm3) was more common in HAdV-2-infected patients (p 0.007). HAdV-7 infections were significantly associated with a longer duration of fever, leucopenia (white blood cell count <5000/mm3), thrombocytopenia (platelet count <150 000/mm3), lower respiratory tract infections, a longer length of hospital stay, and requiring intensive care (all p <0.001).
Childhood HAdV-2, HAdV-3 and HAdV-7 infections may exhibit different clinical manifestations. Although HAdV-3 was the most prevalent genotype observed during the 2011 Taiwan outbreak, HAdV-7 caused more severe disease characteristics and outcomes.
Summary Objective To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and ...the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes. Methods OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes. Results OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage. Conclusions Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.
Accessible summary
The process of nursing professional training may cause emotional stress on nursing students, potentially resulting in depressive symptoms.
As the problems of nurse shortage and ...increase of nursing student graduates who tend not to pursue nursing career continue to exist, it is important for nursing educators to investigate the factors causing depressive symptoms, and further develop strategies to manage their stress and depressive problems.
The prevalence of depressive symptoms among junior college nursing students in Taiwan is high. Grade point average, interest in nursing, interest in clinical placement, career planning after graduation, relieving stress by overeating, sleep quality, stress, and anxiety were correlated with depressive symptoms. Sleep quality, stress, and the degree of anxiety can predict the degree of depressive symptoms among young nursing students in Taiwan.
Development of proper strategies to help young nursing students manage stress, anxiety, and facilitate better learning experiences tailored to their problems and needs may be helpful for alleviation or prevention of depressive symptoms.
Nursing students have particularly experienced stressful lives during nursing education. This cross‐sectional study aimed to investigate depressive symptoms and related factors in junior college nursing students. A total of 625 nursing students from a junior college in Taiwan were assessed by Pittsburgh Sleep Quality Index, Adolescent Depression Inventory, Situational Anxiety Scale and the Taiwanese‐Chinese version of Stress in Nursing Students Scale. The results showed that (1) the prevalence of depressive symptoms among junior college nursing students was 32.6%; (2) depressive symptoms are significantly related to grade point average, interest in nursing, interest in their clinical placement, career planning after graduation, overeating as a stress‐relief strategy, sleep problems, stress, and anxiety; and (3) anxiety, sleep quality, and stress are three major variables that can significantly predict depressive symptoms. Psychological factors may influence young nursing students' willingness to seek assistance from teachers. These factors should be considered when designing strategies to promote their emotional health and well‐being. Nursing educators can plan appropriate strategies tailored to junior college nursing students' problems and needs, which thereby may facilitate learning experience and prevent depressive symptoms.
An estimation, using a Raman spectroscopic technique, of the Young's modulus of a single filament of bacterial cellulose is presented. This technique is used to determine the local molecular ...deformation of the bacterial cellulose via a shift in the central position of the 1095 cm⁻¹ Raman band, which corresponds to the stretching of the glycosidic bond in the backbone of the cellulose structure. By calculating the shift rate with respect to the applied strain it is shown that the stiffness of a single fibril of bacterial cellulose can be estimated. In order to perform this estimation, networks of fibres are rotated through 360° and the intensity of the 1095 cm⁻¹ Raman band is recorded. It is shown that the intensity of this band is largely independent of the angle of rotation, which suggests that the networks are randomly distributed. The modulus is predicted from a calibration of Raman band shift against modulus, using previously published data, and by using Krenchel analysis to back-calculate the modulus of a single fibril. The value obtained (114 GPa) is higher than previously reported values for this parameter, but lower than estimates of the crystal modulus of cellulose-I (130-145 GPa). Reasons for these discrepancies are given in terms of the crystallinity and structural composition of the samples.
Summary Objective To study the effects of oral glucosamine sulfate on the development of osteoarthritis (OA) and to examine concomitant changes in the nociceptive behavior of rats. Methods OA was ...induced in Wistar rats by anterior cruciate ligament transection (ACLT) of the right knee; the left knee was untreated. The OA + glucosamine group received oral glucosamine sulfate (250 mg/kg/day) in a 2-g wafer once a day for 10 consecutive weeks starting at week 5 after ACLT. The OA group was treated as above with 2-g wafers (placebo). The control group of naïve rats received 2-g wafers only. The glucosamine alone group comprised naïve rats receiving glucosamine sulfate only. Nociceptive behavior (mechanical allodynia and weight-bearing distribution of hind paws) during OA development was analyzed pre- and 3, 6, 9, 12, 15, and 18 weeks post-ACLT. Macroscopic and histologic studies were then performed on the cartilage and synovia. Immunohistochemical analysis was performed to examine the effect of glucosamine on expression of mitogen-activated protein kinases (MAPKs) in the articular cartilage chondrocytes. Results OA rats receiving glucosamine showed a significantly lower degree of cartilage degeneration than the rats receiving placebo. Glucosamine treatment also suppressed synovitis. Mechanical allodynia and weight-bearing distribution studies showed significant improvement in the OA + glucosamine group as compared to the OA group. Moreover, glucosamine attenuated p38 and c-Jun N-terminal kinase (JNK) but increased extracellular signal-regulated kinase 1/2 (ERK) expression in OA-affected cartilage. Conclusion Our results indicate that treatment with oral glucosamine sulfate in a rat OA model (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cell p38 and JNK and increase of ERK expression.
Summary
Adjuvant pegylated interferon plus ribavirin treatment (PegIFN/RBV) reduces recurrence and prolongs survival in early stage hepatocellular carcinoma (HCC) patients with chronic hepatitis C ...(CHC) infection receiving resection or ablation. However, the impact of antiviral therapy in intermediate and advanced stage of CHC‐HCC patients is uncertain. This study aimed to investigate the impact PegIFN/RBV treatment on recurrence‐free interval and survival in patients with HCC receiving transarterial chemoembolization (TACE). From 2010 to 2013, 274 CHC patients from a 1073 patient‐based cohort composed of freshly diagnosed HCC and receiving TACE treatment the Chang Gung Memorial Hospital, Linkou Medical Center were recruited. Propensity score matching (PSM) (age, gender, AST to Platelet Ratio Index (APRI), tumour size, tumour number and Child‐Turcotte‐Pugh score) with the ratio 1:2 for patients with and without PegIFN/RBV treatment was performed. Statistics were performed with SPSS V.20 (IBM, USA). After matching, 153 patients were analysed and 27 patients (17.6%) achieved sustained virologic response (SVR). The 2‐year cumulative overall survival rate and recurrence‐free survival rate among patients with SVR, non‐SVR, and untreated were 85.2% vs 58.3% vs 69.6% (P=.001) and 73.3% vs 53.8% vs 58.5% (P=.013). By Cox regression analysis, non‐SVR, untreated, increase CTP score and nonresponder to TACE were independent factors related to mortality. The SVR achieved by PegIFN/RBV treatment markedly improves survival and reduces tumour recurrence in CHC‐HCC patients receiving TACE treatment after complete response.
Summary
Background Hand‐foot skin reaction is a distinctive cutaneous side‐effect of antineoplastic kinase inhibitor‐targeted therapy. Severe hand‐foot skin reaction requires postponement of ...treatment or dose reduction. Histopathological studies of skin toxicity associated with kinase inhibitors are currently unavailable.
Objectives To report the clinical and histopathological findings of hand‐foot skin reaction produced by the multikinase inhibitor sorafenib.
Methods Nine patients with metastatic carcinoma—seven with renal cell carcinoma (RCC), one with melanoma and one with hepatocellular carcinoma (HCC)—received continuous, oral sorafenib 400 mg twice daily. Hand‐foot skin reaction was defined and graded according to National Cancer Institute Common Toxicity Criteria 3.0. Biopsies from lesions of erythematous scaly or blistering skin were obtained from five cases (four RCC and one HCC).
Results Seven of the nine (78%) patients developed hand‐foot skin reaction characterized by well‐demarcated, tender, erythematous papules and plaques with greyish blisters or hyperkeratotic, callus‐like formations on palmoplantar surfaces and distal phalanges. Skin biopsy of hand‐foot skin reaction lesions revealed epidermal acanthosis, papillomatosis, parakeratosis, dispersed dyskeratotic cells and keratinocyte vacuolar degeneration. Other skin toxicities included angular cheilitis, seborrhoeic dermatitis and perianal dermatitis.
Conclusions The clinical manifestations and histopathological features of sorafenib‐induced skin reactions are unique. The most relevant histopathological findings of hand‐foot skin reaction include keratinocyte vacuolar degeneration, the presence of intracytoplasmic eosinophilic bodies, and intraepidermal blisters in the stratum malpighii. Further studies are warranted to elucidate the mechanisms of this novel multitargeted kinase inhibitor‐associated skin reaction.
Summary Background Human enterovirus 71 (HEV71) infections are a significant public health threat in the Asia–Pacific region and occasionally cause severe neurological complications and even death in ...children. Although good hand hygiene is important for controlling infection, relevant data regarding the efficacy of widely used hand disinfectants against HEV71 are still lacking. Aim To investigate the virucidal activity of alcohols and alcohol-based hand disinfectants against HEV71. Methods A common alcohol-based hand disinfectant (0.5% chlorhexidine gluconate + 70% isopropanol) as well as different concentrations of isopropanol and ethanol were tested for virucidal activity against HEV71 using the suspension and the fingerpad tests. Findings In suspension tests, 85% and 95% ethanol achieved a mean log10 reduction factor in HEV71 titre of >3 and nearly 6, respectively, within 10 min. By contrast, 70% and 75% ethanol and any concentration of isopropanol (70–95%) produced a factor of <1 in this test after the same exposure time. In fingerpad tests, only 95% ethanol showed a mean log10 reduction factor of >4, while both 75% ethanol and a chlorhexidine gluconate-containing formula were ineffective against HEV71 with a mean log10 reduction factor of <1 after a 30 s exposure time. Conclusions Widely used alcohol-based hand disinfectants based on 70% ethanol or isopropanol have poor effectiveness against HEV71. Ninety-five percent ethanol is the most effective concentration, but still cannot fully inactivate HEV71 and may be impractical for use in many instances. Hand hygiene with alcohol-based hand disinfectants alone is not recommended for preventing HEV71 transmission.
► A two-model system composing a watershed model and a water quality model was developed. ► The system was developed to simulate the impact of non-point source pollution on water quality. ► The ...system is useful in developing appropriate watershed management strategies.
In this study, an integrated two-model system composed of a multimedia watershed model and a river water quality model was developed to effectively simulate the impacts of non-point source (NPS) pollution on river water quality. NPS pollution loadings from Kaoping River Basin were calculated using the Integrated Watershed Management Model (IWMM). Results from the IWMM modeling were used as the input data for the Kaoping River water quality evaluation using the Water Quality Analysis Simulation Program (WASP) modeling. The land use patterns classified using SPOT images and Digital Elevation Model techniques with the aid of Erdas Imagine® process and ArcView® geographical information system were applied to assist the NPS pollution simulation. Results indicate that land use patterns of orchard farms and farmland areas were the major causes of the NPS pollution, and they should be effectively controlled. Results show that higher flow rates (>200
m
3/s) were observed in the wet seasons, which would cause the increase in NPS pollution loadings. Results demonstrate that the integral approach could develop a direct linkage between upstream land use changes and downstream water quality. Using water quality modeling alone would underestimate the impact of NPS pollution on river water quality. The introduction of the integrated two-model system shows a significant advance in estimating the water quality.
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