PRDM1 promotes the ferroptosis and immune escape of thyroid cancer by regulating USP15-mediated SELENBP1 deubiquitination.

BACKGROUND: The deubiquitinating enzyme Ubiquitin-specific peptidase 15 (USP15) is upregulated in various cancers and promotes tumor progression by increasing the expression of several oncogenes. This project is designed to explore the role and mechanism of USP15 in thyroid cancer (TC) progression. METHODS: Selenium-binding protein 1 (SELENBP1), USP15, CCL2/5, CXCL10/11, IL-4, and TGF-ß1 mRNA levels were detected using real-time quantitative polymerase chain reaction (RT-qPCR). SELENBP1, USP15, GPX4, IL-10, Arg-1, Granzyme B, TNF-α, and PR domain zinc finger protein 1 (PRDM1) protein levels were examined by western blot assay. Fe+ level, malondialdehyde (MDA), and lipid-ROS levels were determined using special kits. The proportion of CD11b+CD206+ positive cells was detected using a flow cytometry assay. The role of SELENBP1 on TC cell growth was examined using a xenograft tumor model in vivo. After GeneMANIA prediction, the interaction between USP15 and SELENBP1 was verified using Co-immunoprecipitation (CoIP) assay. The binding between PRDM1 and USP15 promoter was predicted by JASPAR and validated using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. RESULTS: SELENBP1 was increased in TC subjects and cell lines, and its knockdown repressed TC cell proliferation, migration, invasion, immune escape, and induced ferroptosis in vitro, as well as blocked tumor growth in vivo. In mechanism, USP15 interacted with SELENBP1 and maintained its stabilization by removing ubiquitin. Meanwhile, the upregulation of USP15 was induced by the transcription factor PRDM1. CONCLUSION: USP15 transcriptionally mediated by PRDM1 might boost TC cell malignant behaviors through deubiquitinating SELENBP1, providing a promising therapeutic target for TC treatment.

Can serum IgE or blood eosinophil count predict postoperative oral corticosteroid response in chronic rhinosinusitis with nasal polyps?

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterised by inflammatory mucosa and polyp formation in the paranasal sinuses. The study's primary objective was to evaluate the outcomes of postoperative oral corticosteroid (OCS) in treating patients with bilateral CRSwNP. The secondary objective was to determine whether preoperative serum IgE levels (sIgE)and/or blood eosinophil count (BEC) correlate with postoperative outcomes following OCS use. METHODS: Patients with bilateral CRSwNP (n=236) who underwent endoscopic sinus surgery (ESS) were randomly assigned to receive 15 mg OCS twice daily or a placebo for 2 weeks. We investigated the treatment effects based on the subjective visual analogue scale (VAS), Sino-Nasal Outcome Test 22 (SNOT-22), and objective Lund-Kennedy Endoscopy Score (LKES) over 6 months; subgroups were stratified preoperatively as follows: sIgE <150 IU/mL, sIgE>=150 IU/mL, BEC <0.39x10(9) cells/L, and BEC>=0.39x10(9) cells/L. RESULTS: A total of 193 participants completed the study up to the 6-month follow-up; no apparent linear relationship was noted between sIgE and BEC. No significant differences in scores were noted upon assessment of the VAS, SNOT-22, and LKES among the follow-up timepoints in the primary analysis. However, in the primary or subgroup analyses with sIgE or BEC, significant differences in the longitudinal scores of sleep dysfunction were observed at the 1-month follow-up. CONCLUSION: Postoperative OCS did not significantly affect bilateral CRSwNP outcomes. sIgE levels and BEC may not be surrogate predictive biomarkers to assess the role of postoperative OCS use. OCS may increase the risk of transient sleep disturbance.

[Effect of diurnal temperature range on the number of elderly inpatients with ischemic stroke in Hunan Province].

Objective: To study the effect of diurnal temperature range on the number of elderly inpatients with ischemic stroke in Hunan Province. Method: Demographic and disease data, meteorological data, air quality data, population, economic and health resource data of elderly inpatients with ischemic stroke were collected in 122 districts/counties of Hunan Province from January to December 2019. The relationships between the diurnal temperature range and the number of elderly inpatients with ischemic stroke were analyzed by using the distributed lag non-linear model, including the cumulative lag effect of the diurnal temperature range in different seasons, extremely high diurnal temperature range and extremely low diurnal temperature range. Results: In 2019, 152 875 person-times were admitted to the hospital for ischemic stroke in the elderly in Hunan Province. There was a non-linear relationship between the diurnal temperature range and the number of elderly patients with ischemic stroke, with different lag periods. In spring and winter, with the decrease in diurnal temperature range, the risk of admission of elderly patients with ischemic stroke increased (Ptrend<0.001, Ptrend=0.002);in summer, with the increase in diurnal temperature range, the risk of admission of elderly patients with ischemic stroke increased (Ptrend=0.024);in autumn, the change in the diurnal temperature range would not cause a change in admission risk (Ptrend=0.089). Except that the lag effect of the extremely low diurnal temperature range in autumn was not obvious, the lag effect occurred in other seasons under extremely low and extremely high diurnal temperature ranges. Conclusion: The high diurnal temperature range in summer and the low diurnal temperature range in spring and winter will increase the risk of admission of elderly patients with ischemic stroke, and the risk of admission of elderly patients with ischemic stroke will lag under the extremely low and extremely high diurnal temperature ranges in the above three seasons.

Circ_0059354 aggravates the progression of papillary thyroid carcinoma by elevating ARFGEF1 through sponging miR-766-3p.

BACKGROUND: Circular RNAs (circRNAs) have been identified as vital players in tumors, including papillary thyroid carcinoma (PTC). The purpose of this study is to explore the functions of circ_0059354 on PTC development. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the levels of circ_0059354, microRNA-766-3p (miR-766-3p) and ADP ribosylation factor guanine nucleotide exchange factor 1 (ARFGEF1). Cell Counting Kit-8 (CCK-8) assay and colony formation assay were proceeded for cell proliferation ability. Transwell assay was conducted for cell migration and invasion. Tube formation assay was employed to examine the angiogenesis ability. Flow cytometry analysis was adopted for cell apoptosis. Western blot assay was conducted for protein levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized to verify the relationships among circ_0059354, miR-766-3p and ARFGEF1. The murine xenograft model was constructed to analyze the function of circ_0059354 in vivo. RESULTS: Circ_0059354 level was abnormally increased in PTC tissues and cells. Functionally, circ_0059354 silencing suppressed cell proliferation, migration, invasion and angiogenesis and facilitated apoptosis in PTC cells. Circ_0059354 was identified to sponge miR-766-3p, which directly targeted ARFGEF1. Moreover, circ_0059354 directly targeted miR-766-3p to positively regulated ARFGEF1 expression. MiR-766-3p inhibition reversed circ_0059354 knockdown-mediated effect of PTC cell malignant behaviors. Overexpression of miR-766-3p restrained the malignant behaviors of PTC cells, whereas ARFGEF1 elevation reversed the effects. Additionally, circ_0059354 deficiency blocked tumor growth in vivo. CONCLUSION: Circ_0059354 served as an oncogene in PTC progression through regulating miR-766-3p/ARFGEF1 axis.

[Efficacy and safety of belimumab treatment in childhood-onset systemic lupus erythematosus].

Objective: To evaluate the efficacy and safety of belimumab in children with systemic lupus erythematosus (cSLE). Methods: The clinical data of 49 cSLE patients admitted into the Department of Rheumatology and Immunology, Children's Hospital affiliated to the Capital Institute of Pediatrics, from August 2018 to December 2021 were collected. They were divided into the belimumab treatment group (18 cases) and the traditional treatment group (31 cases) according to whether they received belimumab treatment. The cSLE patients in the traditional group had similar baseline SLEDAI scores with the belimumab group and were treated with traditional immunosuppressive drugs. The clinical symptoms and improvements before and after treatment, as well as the differences in adverse events during follow-up were compared between the two groups. Results: In belimumab group, the age was (11.9±1.8) years old, the median (Q1, Q3) of disease duration was 7.5 (2.0, 16.8) months, 3 patients were male, and 15 patients completed 24 weeks of treatment. In the traditional treatment group, 31 patients with cSLE were enrolled, with an average age of (11.3±2.4) years, a median (Q1, Q3) of disease duration of 7.0 (2.5, 10.5) months, among whom 6 patients were male, and 25 patients completed 24 weeks of treatment. At baseline, the belimumab treatment group had a significantly lower oral prednisone dose than the conventional treatment group [(29.58±12.43) mg/d vs (38.20±14.11) mg/d, P=0.037]. After 24 weeks of treatment, the dosage of prednisone in both groups was reduced, and the dosage of prednisone in the belimumab group was (14.12±5.86) mg/d, which was lower than that in the traditional treatment group [(23.51±9.79) mg/d] (P=0.002). After 24 weeks of treatment, the levels of complement C3 and C4 increased, the dsDNA levels and SLEDAI score decreased in both groups (all P>0.05). The incidence of adverse events in belimumab group (3/15, 3 cases) was lower than that in traditional treatment group (32.0%, 8/25) (P>0.05). Conclusions: Belimumab in the treatment of cSLE can reduce the initial dose of prednisone and facilitate the reduction of prednisone dose, significantly improve the clinical symptoms and organ involvement, and reduce the disease activity. The incidence of adverse events was low during belimumab treatment.

[Effects of parity on nutrition and health status of Chinese women of childbearing age].

Objective: To analyze effects of parity on women's nutrition and health status. Methods: This study was based on the data bank of "Chinese Nutrition and Health Surveillance of Children and Adolescents Aged 0-17 years old and Lactating Mothers from 2016 to 2017". Using a multi-stage stratified random sampling method, 17 771 women at 0 to 24 months postpartum from 31 provinces in Mainland China were included in this study. Questionnaires were used to collect data on women's general demographic characteristics, parity, mode of delivery, pre-pregnancy weight, pre-delivery weight, diseases before and during pregnancy, postpartum hemorrhage. Current body height, body weight, waist circumference, and blood pressure were measured. Blood hemoglobin, blood glucose and blood lipids were detected. Pre-pregnancy BMI, gestational weight gain, postpartum weight retention, postpartum BMI, the rates of anemia, hypertension, diabetes, and dyslipidemia were calculated. Survey sample weights were calculated according to the sampling design and number of children under 2 years old from the sixth population census data of China. Effects of parity on the observational indicators after adjusting for confounding factors were analyzed by multivariate linear regression and multivariate logistic regression. Results: The age of 17 771 women was (29.5±5.0) years old, 12.2% (2 172) were over 35 but less than 40 years old, and 3.2% (563) were over 40 years old; the women with one parity, two parities, and three parities accounted for 47.3% (8 413), 48.5% (8 620) and 4.2% (738), respectively; urban women accounted for 49.9% (8 875), and rural women accounted for 50.1% (8 896). The results from multivariate linear regression showed that the pre-pregnancy BMI of women with two and three parities was 0.55 kg/m2 and 0.76 kg/m2 higher than women with one parity, respectively; the results of multivariate logistic regression showed that the OR(95%CI) of pre-pregnancy anemia was 1.45(1.04-2.02) for women with three parities compared with women with one parity, and the OR(95%CI) of anemia during pregnancy for women with two parities was 1.20(1.06-1.35) compared with women with one parity. Conclusion: Parity is associated with pre-pregnancy BMI and risk of anemia before and during pregnancy in women of reproductive age.

[Determination of 6 BTEXs in urine by purge and trap with gas chromatography-mass spectrometry].

Objective: To establish a method for detection of 6 BTEXs in urine by Purge and Trap-Gas Chromatography-Mass Spectrometry. Methods: The urine sample need not be diluted, but directly purge and trap in the bottle, separated by gas chromatography column, then simultaneously analyzed by retention time locking (RTL) method and selective ion scanning mode (SIM) . Results: The linear range of 6 BTEXs in urine was good, the correlation coefficient was between 0.997 4 and 0.998 9. The minimum quantification limits was 0.010-0.036 µg/L. The precision was 1.9%-4.7%, and the recovery was 93.1%-101.9%. Conclusion: The method has the advantages of wide linear range, high sensitivity and recovery. It is suitable for the determination of 6 BTEXs in urine of low level occupational-exposed or non-exposed population.

[Determination of six benzene homologues in human blood by purge and trap-gas chromatography-mass spectrometry].

Objective: To establish a purge and trap-gas chromatography-mass spectrometry method based on soil analysis model for the determination of six benzene homologues (benzene, toluene, ethylbenzene, m-xylene, p-xylene and o-xylene) in human blood. Methods: From September 2020 to May 2021, diatomite was used as a dispersant to add 2.0 ml blood sample and fully mixed. The sample was directly injected into the purging and collecting bottle after purging. The gas chromatography column was used for separation. The retention time locking was used for qualitative analysis and the selected ion scanning mode (SIM) was used for detection. The detection limit and recovery rate of the method were analyzed. Results: The linear range of the method for the determination of six benzene homologues in human blood was 0.02-10.00 ng/ml, the correlation coefficient was 0.9927-0.9968, the detection limit was 0.006-0.016 ng/ml, the recovery rate of sample spiking was 84.39%-102.41%, and the precision of the method was 3.06%-6.90%. Conclusion: Purge and trap-gas chromatography-mass spectrometry can simultaneously determine the contents of six benzene homologues in human blood. The pretreatment method is simple, time-saving, and the method has low detection limit, which provides a scientific basis for the detection of benzene homologues in human body.

Characteristics and impacts of itch in children with inflammatory skin disorders.

BACKGROUND: Itch is a cardinal feature of paediatric disorders and can impair quality of life. However, few studies have addressed symptoms and impacts of itch in paediatric patients. OBJECTIVES: We focused on understanding the child's experience of itch and the impact of itch specifically on affected children, including comparison with the adult experience. METHODS: Semistructured interviews (nine parents, 15 children with itch) explored concerns related to paediatric itch experiences and effects. Themes were compared with those of previous adult interviews. Literature was reviewed to identify the need for a more comprehensive measure of paediatric itch. RESULTS: Itch quality, intensity, duration and environmental triggers (sweating, climate change, stress and certain fabrics) are important aspects of the child's itch experience. Skin disruption, physical function, concentration, emotional reactions, stigma and relationships/social effects are itch impact themes that emerged. No paediatric-specific scale comprehensively captures the paediatric patient itch experience. However, differences between child and adult reports of itch-related pain, functional limitations, fatigue and restlessness, emotional reactions to itch, and treatment effects emphasize the need for a paediatric-specific measurement tool. CONCLUSIONS: Children and parents endorse the importance of capturing the paediatric-focused characteristics and impacts of itch in measuring disease severity and response to intervention.

Association of MICA gene polymorphisms with thionamide-induced agranulocytosis.

BACKGROUND: Thionamide-induced agranulocytosis (TIA), namely antithyroid drug (ATD)-induced agranulocytosis, is one of the most feared adverse effect of ATDs. It is defined as a granulocyte count of less than 0.5 × 109/L after ATD administration. Several studies reported that TIA is associated with human leukocyte antigen (HLA) and nearby genes. Our previous study found that the susceptibility genes of TIA are similar in north China and European populations. METHODS: We evaluated the associations of 23 candidate single nucleotide polymorphisms (SNPs) in 37 patients with TIA and 254 patients with Graves' disease (GD) as controls by iPLEX MassARRAY system. RESULTS: Five SNPs in the MHC class I polypeptide-related sequence A(MICA) genes [rs4349859 (p = 1.43E-7); rs145575084 (p = 5.79E-6); rs116135464 (p = 3.70E-5); rs148015908 (p = 3.79E-5) and rs189600525 (p = 2.15E-4)] were found to be significantly associated with TIA after Bonferroni correction. After combining with previous data of rs4349859 and HLA-B*27:05, the haplotype analysis showed that patients carrying P-A-C-A-T-T-A haplotype have a higher risk of TIA (p = 9.76E-7; OR = 14.85, 95% CI 3.63-60.77). CONCLUSION: Our findings suggest that five high linked SNPs of MICA gene are significantly associated with susceptibility to TIA.

Association of prurigo nodularis and infectious disease hospitalizations: a national cross-sectional study.

BACKGROUND: Prurigo nodularis (PN) is associated with a variety of systemic comorbidities, including infectious diseases such as HIV and viral hepatitis. There are limited data on other infectious disease comorbidities in patients with PN. AIM: To characterize infectious disease hospitalizations among patients with PN and the associated cost burden. METHODS: We searched the 2016-2017 National Inpatient Sample, a cross-sectional sample of 20% of all US hospitalizations, for infectious disease hospitalizations among patients with PN. Associations of PN with infections and related costs were determined using multivariable logistic and linear regression, adjusting for age, race, sex and insurance type. RESULTS: PN was associated with any infection overall (OR = 2.98, 95% CI 2.49-3.56), and with HIV, cutaneous, hepatobiliary, central nervous system, bacterial, viral and fungal/parasitic infections and for sepsis. Patients with PN had a higher mean cost of care (US$11 667 vs. US$8893, P < 0.001) and length of stay (5.5 vs. 4.2 days, P < 0.001) for any infection overall and for 7 of 13 other infections. Adjusting for age, race, sex and insurance coverage, PN was associated with higher cost (+30%, 95% CI +17 to +44%) and higher length of stay (+30%, 95% CI +18 to +44%) for any infection overall, and for several specific infections. These associations remained with alternate regression models adjusting for severity of illness. CONCLUSION: There is a high infectious disease burden among patients with PN, corresponding to higher healthcare utilization and spending. Clinicians must be aware of these associations when treating these patients with immunomodulatory drugs.

Does geodemographic segmentation explain differences in route of cancer diagnosis above and beyond person-level sociodemographic variables?

BACKGROUND: Emergency diagnosis of cancer is associated with poorer short-term survival and may reflect delayed help-seeking. Optimal targeting of interventions to raise awareness of cancer symptoms is therefore needed. METHODS: We examined the risk of emergency presentation of lung and colorectal cancer (diagnosed in 2016 in England). By cancer site, we used logistic regression (outcome emergency/non-emergency presentation) adjusting for patient-level variables (age, sex, deprivation and ethnicity) with/without adjustment for geodemographic segmentation (Mosaic) group. RESULTS: Analysis included 36 194 and 32 984 patients with lung and colorectal cancer. Greater levels of deprivation were strongly associated with greater odds of emergency presentation, even after adjustment for Mosaic group, which nonetheless attenuated associations (odds ratio [OR] most/least deprived group = 1.67 adjusted [model excluding Mosaic], 1.28 adjusted [model including Mosaic], P < 0.001 for both, for colorectal; respective OR values of 1.42 and 1.18 for lung, P < 0.001 for both). Similar findings were observed for increasing age. There was large variation in risk of emergency presentation between Mosaic groups (crude OR for highest/lowest risk group = 2.30, adjusted OR = 1.89, for colorectal; respective values of 1.59 and1.66 for lung). CONCLUSION: Variation in risk of emergency presentation in cancer patients can be explained by geodemography, additional to deprivation group and age. The findings support proof of concept for public health interventions targeting all the examined attributes, including geodemography.

Evaluating OzHarvest's primary-school Food Education and Sustainability Training (FEAST) program in 10-12-year-old children in Australia: protocol for a pragmatic cluster non-randomized controlled trial.

BACKGROUND: The promotion of healthy eating is a public health priority. Poor dietary behaviours, including low fruit and vegetable (F&V) consumption are of particular concern among children. Novel nutrition promotion strategies are needed to improve F&V consumption. Sustainability education could be used to support nutrition education within the school context. The purpose of this paper is to report the protocol for impact and process evaluation of the school-based Food Education and Sustainability Training (FEAST) program, designed to educate children about sustainability, food waste and nutrition, using hands-on cooking activities. METHODS: A pragmatic, parallel, cluster non-randomized controlled trial with pre- and post-measures, will be implemented among 20 primary schools (10 intervention vs 10 wait-list-control) within NSW, Australia, involving children in Grades 5-6. FEAST is a curriculum-aligned program, delivered as a 1.5-h lesson/week, for a 10-week unit of inquiry, incorporating theory and cooking. FEAST was developed using theoretical frameworks which included Social Cognitive Theory and the Precede-Proceed Planning model. Primary outcomes include children's self-reported F&V intakes (serves/day). Food literacy constructs such as: nutrition knowledge, food preparation and cooking skills, self-efficacy and behaviours, food waste knowledge and behaviours and food production knowledge, will be assessed as secondary outcomes. Process evaluation will assess program reach, adoption, implementation, maintenance, satisfaction and perceived benefits by teachers and students. An online survey (including quantitative and qualitative questions) was developed for administration at baseline (impact evaluation) and immediately post-intervention (impact and process evaluation). Intervention effects on quantitative study outcomes will be estimated with ​generalised linear mixed models, including random effects and will follow the intention-to-treat principles. Open-ended questions embedded within the surveys will be analysed qualitatively using content and thematic analyses. DISCUSSION: Results from this trial will provide valuable information on the value of adding environmental sustainability strategies to nutrition education in schools. Results will inform the design of future research and programs focused on primary-school children's nutrition, sustainability-related behaviours and experiential school-based interventions. TRIAL REGISTRATION: Trial registered 14th December 2020 with the Australian and New Zealand Clinical Trials Registry ( ACTRN12620001347954 ).

[Therapeutic effects of sacral neuromodulation on detrusor underactivity].

OBJECTIVE: To evaluate the effects of sacral neuromodulation (SNM) on detrusor underactivity (DUA). METHODS: From December 2019 to April 2020, 6 patients with DUA who had been treated with SNM were assessed retrospectively. The average age was 58 years (46-65 years), with 3 males and 3 females. All the patients were diagnosed with DUA by urodynamics examination. Obstruction of bladder outlet was excluded through the cystoscopy. No patient had the history of neurological disease. All the patients were placed with the bladder colostomy tube before SNM. One female patient accepted the trans-urethral resection of bladder neck. Two male patients accepted the trans-urethral resection of prostate. All the 3 patients had no improvement of void symptom after the urethral operation. Before SNM, the average 24 h times of voiding was 23.8 (18-33), average volume of every voiding was 34.2 mL (10-50 mL), average residual volume was 421.7 mL (350-520 mL). The preoperative and postoperative 24 h urine frequency, average voided volume, and average residual urine volume were compared respectively. RESULTS: Totally 6 patients underwent SNM with stage Ⅰ procedure. The operation time for stage Ⅰ procedure was 62-135 min (average 90 min). After an average follow-up of two weeks, stage Ⅱ procedure was performed on responders. Four patients accepted stage Ⅱ procedure (conversion rate 66.7%), the other two patients refused the stage Ⅱ procedure because the urine frequency did not reach the satisfied level. But all the patients had the improvement of residual urine volume. For the 4 patients at the follow-up of 10-15 months, the improvement of void was still obvious. For the all patients after stage Ⅰ procedure, the average 24 h urine frequency reduced to 13.5 times (9-18 times, P < 0.001), the average voided volume increased to 192.5 mL (150-255 mL, P < 0.001), and the average residual urine volume reduced to 97.5 mL (60-145 mL, P < 0.001). No adverse events, such as wound infection or electrode translocation were detected during an average follow-up of 11.3 months. Only one of the 4 patients who received the stage Ⅱ procedure did the intermittent catheterization for one time each day. CONCLUSION: SNM provides a minimal invasive approach for the management of DUA.

[Modified posteromedial approach via lateral side of flexor hallucis longus for the treatment of posterior Pilon fracture].

Objective: To compare the clinical efficacy and the level of muscle and soft tissue damage between modified posteromedial approach via lateral side of flexor hallucis longus and modified posteromedial approach in the treatment of posterior Pilon fracture. Methods: Total of 43 patients (27 males and 16 females, aged from 19 to 71 years) diagnosed with posterior Pilon fracture from June 2016 to June 2018 in Foshan Hospital of Traditional Chinese Medicine were randomly divided into observation group (modified posteromedial approach via lateral side of flexor hallucis longus, 21 cases) and control group (modified posteromedial approach, 22 cases) according to the operation approach. The preoperative waiting time, intraoperative time, intraoperative blood loss, hospitalization time and the complications were recorded and compared between the two groups. The differences of blood creatine kinase (CK), myoglobin (Myo) and C-reactive protein (CRP) at different time points before and after operation were compared between the two groups to elevate the level of muscle and soft tissue damage. The fracture reduction qualities of the two groups were compared by Burwell-Charnley criteria. The differences of fracture healing time, range of motion of metatarsophalangeal joint of the great toe (MTP-ROM), ankle range of motion (Ankle-ROM), American Orthopaedic Foot & Ankle Society (AOFAS) score and visual analogue scale (VAS) score of pain were compared between the two groups at the last follow-up. Results: The observation group and the control group were followed-up for (19±6) months and (16±8) months, respectively; there was no significant difference between the two groups (P>0.05). There were no significant differences in preoperative waiting time, intraoperative blood loss, hospitalization time and fracture healing time between the two groups (all P>0.05). At the last follow-up, there was no significant difference in the MTP-ROM and Ankle-ROM between the two groups (both P>0.05); the AOFAS score of the observation group was 88.2±7.8 and it was 84.5±7.6 in the control group (P>0.05); the VAS score of the observation group was (0.9±1.0) and it was (1.3±0.8) in the control group(P>0.05). Anatomical reduction rate in observation group was higher than that in control group (90.5% vs 81.8%, P>0.05). The operation time in the observation group was (87±16) min and it was (98±11) min in the control group (P<0.05). CK, Myo and CRP were increased in both groups after surgery, but there was no statistical significance between groups at the same time point (all P>0.05). There was no nerve injury in the observation group, while 2 cases (9.0%) of nerve paralysis occurred in the control group. No incision infection and checkrein deformity of the Hallux was found in the two groups. Conclusion: The modified posteromedial approach via lateral side of flexor hallucis longus can obtain good operative field exposure, and does not increase muscle and soft tissue injury, with shorter operative time and fewer complications, without nerve injury and checkrein deformity, it is a safe approach for the treatment of posterior Pilon fracture.

[Clinical and imaging characteristics of patients with primary cardiac angiosarcoma].

Objective: To investigate the clinical, cardiac imaging characteristics and prognosis of patients with primary cardiac angiosarcoma. Methods: The clinical data of 14 patients hospitalized with primary cardiac angiosarcoma from January 2001 to December 2017 in Peking Union Medical College Hospital were collected and analyzed. Metastatic cardiac angiosarcoma was not included in this study. Patients were followed up post discharge per telephone call or clinical visit. Results: Of the 14 patients, 8 were males and 6 were females, average age was 48 years. The main clinical symptoms were shortness of breath (8/14), hemoptysis (6/14), fever (5/14), chest pain (4/14) and cough (3/14). Imaging examinations showed that the tumors of 8 patients were located in the right heart and 6 in the pericardial cavity. Tumors in the right heart often infiltrate the atrial wall and cause pericardial effusion (7/8). Tumors in the pericardium were characterized by recurrent bloody pericardial effusion (6/6), prone to progressive constrictive pericarditis (3/6), pericardial fluid cytology was often negative (6/6). MRI showed heterogeneous high signal intensity (cauliflower aspect) on T2-weighted image and heterogeneous enhancement with a"sunray" aspect at the perfusion study. At the time of diagnosis, 8 patients developed lung or adrenal metastasis (8/14). The median survival was only 305 days. Conclusions: Primary cardiac angiosarcoma is a rare disease with non-specific clinical manifestation and poor prognosis. Imaging examinations may help diagnosis. The high invasiveness and the easy-to-metastasis feature of the tumor contribute to the poor prognosis of cardiac angiosarcoma.

Evaluation of responsiveness and estimation of smallest detectable change and minimal important change scores for the Childhood Atopic Dermatitis Impact Scale.

BACKGROUND: The Childhood Atopic Dermatitis Impact Scale (CADIS) is an instrument to measure quality of life in young children affected by atopic dermatitis, and their parents. OBJECTIVES: To evaluate the responsiveness (sensitivity to change), smallest detectable change (SDC) and minimal important change (MIC) of the CADIS. METHODS: Parents and primary caregivers of 300 young children completed the CADIS and a global rating of their child's skin condition at baseline and a 4-week follow-up. Kruskal-Wallis tests, Wilcoxon tests and effect sizes were used to assess responsiveness. The SDC can be seen as a change beyond measurement error. Anchor-based and distribution-based methods, and an integration of both methods were used to estimate the MIC. RESULTS: In total, 270 families provided data at baseline and 228 at follow-up. The CADIS total change score and most of the domain scores had moderate-to-strong correlations with the skin change score. Patients were grouped according to the skin change score, which served as an anchor. Children whose parents noted an improvement of the skin showed lower CADIS scores at follow-up (P < 0·001). For the SDC we obtained score changes of 1·34 points on the total score and < 1·0 points on each domain score. All detected MIC values passed the SDC cut-off. CONCLUSIONS: The CADIS is sensitive to change towards improvement of quality of life. A change > 12% on the total score or each domain score very likely represents a clinically important change. What's already known about this topic? Atopic dermatitis reduces the quality of life of affected children and their parents. The Childhood Atopic Dermatitis Impact Scale (CADIS) has been evaluated and translated into two further languages. What does this study add? Further validation of the responsiveness of the CADIS, and whether it is sensitive to change in patients whose condition had changed. Calculation of the smallest detectable change. What are the clinical implications of this work? Estimation of the minimal important change in CADIS provides benchmarks for clinical practice.

Measurement properties of the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire: itch severity assessments in adults with atopic dermatitis.

BACKGROUND: Little is known about the validity of numeric rating scales (NRS) and verbal rating scales (VRS) for itch and itch frequency for assessing itch severity in atopic dermatitis (AD). We evaluated the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire (PIQ) - itch severity assessment, including multiple NRS, VRS and frequency of itch assessments, in adults with AD and compared their performance. METHODS: Self-administered questionnaires and skin examinations were performed in 410 patients with AD (aged 18-90 years) in a dermatology practice setting. RESULTS: PIQ NRS, VRS and frequency of itch had good content validity, strong correlations with one another (Spearman correlations P < 0·001) and weak-to-moderate correlations with patient-oriented eczema measure (POEM), Eczema Area and Severity Index (EASI), objective SCORing AD (SCORAD) and Dermatology Life Quality Index (DLQI) (P < 0·001) and very good discriminant validity. Changes from baseline in NRS, VRS and frequency of itch were moderately to strongly correlated with one another, and weakly to moderately correlated with other patient-reported (POEM, SCORAD itch, DLQI) and clinician-reported outcomes (EASI, objective SCORAD). NRS and VRS worst itch and average itch showed moderate-to-good test-retest reliability. There were no floor or ceiling effects for NRS or VRS itch, but there were ceiling effects for itch frequency. Each assessment was completed in < 1 min by all patients. CONCLUSIONS: NRS, VRS and frequency of itch items from PIQ - itch severity showed good content and construct validity, reliability, and/or responsiveness in adults with AD, and were feasible for use in clinical trials and practice. What is already known about this topic? Numeric rating scales (NRS), verbal rating scales (VRS) and frequency of itch have been used to assess the burden of itch. However, there have been limited results demonstrating their validity, responsiveness, interpretability and feasibility, particularly in atopic dermatitis (AD). What does this study add? This study demonstrated that NRS, VRS and frequency of itch items from the Patient-Reported Outcomes Information System (PROMIS® ) Itch Questionnaire (PIQ) - itch severity assessments had good construct validity, responsiveness, reliability and feasibility in the assessment of adult AD. PIQ NRS, VRS and frequency of itch all appear to have sufficient validity, reliability and feasibility for use as assessments of itch in adults with AD in clinical practice and trials. What are the clinical implications of this work? PIQ NRS and VRS are all simple, valid, reliable and feasible for use in clinical practice and trials to assess itch in adults with AD. Linked Comment: Oosterhaven. Br J Dermatol 2020; 183:802-803.

Antiretroviral Adherence, Drug Resistance, and the Impact of Social Determinants of Health in HIV-1 Patients in the US.

Adherence to antiretroviral therapy (ART) is critical to achieving viral suppression. However, social determinants of health (SDoH) can undermine patient adherence to ART, resulting in drug resistance that compromises future treatment options. We assessed ART adherence and HIV-1 drug resistance at the national and state levels in the US and investigated their associations with SDoH and other HIV-related outcomes. Data were obtained from Symphony Health's Integrated Dataverse (IDV), Monogram/LabCorp Database, as well as national and publicly available databases, including Centers for Disease Control and Prevention (CDC), American Community Survey (ACS), and J. Kaiser Family Foundation (KFF). Inferential analyses were performed to investigate associations using patient-level data, and the results were reported by state and overall within the nation. Correlations between continuous variables were estimated by the Spearman's test, and that between continuous variable and categorical variable were estimated using one-way analysis of variance (ANOVA). State-level rates of poor adherence and resistance ranged from 26 to 55% and 20 to 54%, respectively. Female gender, non-white race, low education, poverty, and unemployment were associated with poor adherence; female gender was associated with drug resistance. Both adherence and resistance were correlated to HIV prevalence rates. Our findings suggest that US patients living with HIV face great challenges associated with poor ART adherence and HIV-1 drug resistance.

Development of a validated short-form of the Childhood Atopic Dermatitis Impact Scale, the CADIS-SF15.

BACKGROUND: The Childhood Atopic Dermatitis Impact Scale (CADIS) with 45 items may be burdensome to complete. We therefore aimed to develop a CADIS short-form. METHODS: Parents of 300 children completed the prototype CADIS. Exploratory factor analysis was conducted on the 45-item CADIS version. The most representative items were chosen. Confirmatory factor analysis was used to confirm the a priori factor structure. Content validity was assessed in a focus group of patients, parents, clinicians, methodologists and industry delegates. Internal consistency, 48-h test-retest reliability, construct validity and responsiveness of the newly developed short-form were assessed. RESULTS: A total of 270 families provided data at baseline, 34 after 48 h and 228 after 4 weeks. Fourteen items of three different factors fulfilled the proposed eligibility criteria and were included in the draft short-form. After the content validity rating, one item relating to the child's sleep was added to further improve content validity. The confirmatory factor analyses showed good model fit, and a 15-item short-form was initiated, the CADIS-SF15. The total scale and the three domains showed good internal consistency and test-retest reliability. The correlation between SCORAD and other subjective measures was consistent with our hypotheses. Differences in scores between mild, moderate and severe AD patients were significant, and the CADIS-SF15 was able to detect changes in 'improving' patients over time. CONCLUSION: The CADIS-SF15 with 15 items in three domains is an internally consistent, reliable, valid, responsive and brief measure of QoL in children affected with AD and their parents. Further evaluation of clinical applicability is required.