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Among the 14.6% of American households experiencing food insecurity, approximately 2 million are occupied by older adults. Food insecurity among older adults has been linked to poor health, lower cognitive function, and poor mental health outcomes. While evidence of the association between individual or household-level factors and food insecurity has been documented, the role of neighborhood-level factors is largely understudied. This study uses data from a representative sample of 1,870 New York City senior center participants in 2008 to investigate the relationship between three neighborhood-level factors (walkability, safety, and social cohesion) and food insecurity among the elderly. Issues relating to food security were measured by three separate outcome measures: whether the participant had a concern about having enough to eat this past month (concern about food security), whether the participant was unable to afford food during the past year (insufficient food intake related to financial resources), and whether the participant experienced hunger in the past year related to not being able to leave home (mobility-related food insufficiency). Unadjusted and adjusted logistic regression was performed for each measure of food insecurity. Results indicate that neighborhood walkability is an important correlate of mobility-related food insufficiency and concern about food insecurity, even after controlling the effects of other relevant factors. [ABSTRACT FROM AUTHOR]

Background: The localization in tumor tissue of various markers by immunohistochemistry can help to establish a diagnosis or predict prognosis. Nitric oxide is associated with tumors and has been studied indirectly by nitrotyrosine analysis and with use of the enzymes nitric oxide synthase (NOS)1, NOS2, and NOS3. Nitric oxide reacts with superoxide anions to yield peroxynitrite, which has toxic effects on genes. Peroxynitrite adds a nitro group to the benzene ring of tyrosine to form nitrotyrosine. The accumulation of nitrotyrosine, a stable product in cells, indicates the formation of peroxynitrite. Nitric oxide stimulates the production of cyclooxygenase-2 (COX-2), which has been associated with angiogenesis in tumors. Neovascularization influences tumor prognosis, as demonstrated by microvessel studies with use of CD34, an immunohistochemical endothelial cell marker. This study examines the expression of these markers in chondrosarcomas and their relation to histological grade and prognosis.Methods: Tissue microarrays composed of formalin-fixed tissue samples from 101 patients with chondrosarcoma were immunohistochemically stained to localize NOS1, NOS2, NOS3, COX-2, nitrotyrosine, and CD34. Five samples of normal cartilage were used as controls. Patient demographics, selected surgical variables, and tumor grade were tabulated, and the associations were analyzed. Analyses of local and overall survival rates were performed with use of the Kaplan-Meier method, and multivariable analyses were performed.Results: There was a significant association of nitrotyrosine, COX-2, and CD34 with histological grades (p = 0.022, p = 0.014, and p = 0.028, respectively), but not with overall prognosis (p = 0.064, p = 0.143, and p = 0.581, respectively). The presence of NOS2 was associated with a lower rate of local disease-free survival (p = 0.038), and positive expressions of NOS1 and NOS2 were associated with decreased overall survival rates (p = 0.007 and p < 0.001, respectively). On multivariable analysis, NOS2 expression demonstrated an independent prognostic impact on local disease-free survival; NOS1 and NOS2 expression was a dependent variable, and their isolated or combined expression was related to lower overall survival rates (p = 0.046 and p = 0.004) (hazard ratio, 3.17 [95% confidence interval, 1.0 to 9.8] and 5.58 [95% confidence interval, 1.7 to 18.0], respectively).Conclusions: Immunohistochemical markers may have an independent value in predicting the prognosis for patients with chondrosarcoma. [ABSTRACT FROM AUTHOR]

Background/aims: Hyperuricemia plays an essential role in the gout. Despite the clinical significance of hyperuricemia, a direct relationship between oral health and hyperuricemia has not been established. We aim to investigate the association between oral health and hyperuricemia., Methods: We selected 17,557 subjects from the Korea National Health and Nutrition Examination Survey database for the years 2016-2019. Oral health-related variables included the number of dental caries, regular tooth brushing, use of secondary oral products, and regular dental examinations. The odds ratio (OR) and 95% confidence intervals (CIs) for hyperuricemia were calculated using a multivariable-adjusted logistic regression model., Results: Oral health status with dental caries and oral health behaviors, including tooth brushing, secondary oral products, and regular dental examination, were significantly associated with hyperuricemia in all participants. The adjusted OR and 95% CIs for hyperuricemia comparing more than three dental caries with no dental caries were 1.28 (1.08-1.52). The adjusted OR and 95% CIs for hyperuricemia in regular tooth brushing, use of secondary oral products, and regular dental examination were 0.78 (0.67-0.91), 0.91 (0.83-1.00), and 0.86 (0.78-0.95), respectively. Notably, the association between oral health and hyperuricemia was more prominent in male subjects. In addition, when subjects were grouped by the oral health scoring system, the prevalence of hyperuricemia was lower in groups with better oral health scores., Conclusion: We demonstrated that oral health status and behaviors are associated with hyperuricemia, particularly in males. Further studies are necessary to confirm the association between oral health and hyperuricemia.

Background: Thumb carpometacarpal joint (CMC) osteoarthritis is the most symptomatic hand arthritis but the long-term healthcare burden for managing this condition is unknown. We sought to compare total healthcare cost and utilisation for operative and nonoperative treatments of thumb CMC arthritis. Methods: We conducted a retrospective longitudinal analysis using a large nationwide insurance claims database. A total of 18,705 patients underwent CMC arthroplasty (trapeziectomy with or without ligament reconstruction tendon interposition) or steroid injections between 1 October 2015 and 31 December 2018. Primary outcomes, healthcare utilisation and costs were measured from 1 year pre-intervention to 3 years post-intervention. Generalised linear mixed effect models adjusted for potentially confounding factors such as the Elixhauser comorbidity score with propensity score matching were applied to evaluate the association between the primary outcomes and treatment type. Results: A total of 13,646 patients underwent treatment through steroid injections, and 5,059 patients underwent CMC arthroplasty. At 1 year preoperatively, the surgery group required $635 more healthcare costs (95% CI [594.28, 675.27]; p < 0.001) and consumed 42% more healthcare utilisation (95% CI [1.38, 1.46]; p < 0.0001) than the steroid injection group. At 3 years postoperatively, the surgery group required $846 less healthcare costs (95% CI [-883.07, -808.51], p < 0.0001) and had 51% less utilisation (95% CI [0.49, 0.53]; p < 0.0001) annually. Cumulatively over 3 years, the surgical group on average was $4,204 costlier than its counterpart secondary to surgical costs. Conclusions: CMC arthritis treatment incurs high healthcare cost and utilisation independent of other medical comorbidities. At 3 years postoperatively, the annual healthcare cost and utilisation for surgical patients were less than those for patients who underwent conservative management, but this difference was insufficient to offset the initial surgical cost. Level of Evidence: Level III (Therapeutic).

Background: Traumatic hand injuries often present with high acuity, but little is known about the influence of geospatial and socioeconomic factors on the timely delivery of care., Methods: This cross-sectional study used the Michigan Trauma Quality Improvement Program database, a state-wide registry with 35 level I or II trauma centers. Adult patients sustained hand trauma requiring urgent operative treatment between 2016 and 2021. Zip codes of injury location were linked with the corresponding percentile score on the Area Deprivation Index (ADI), a comprehensive measure of neighborhood disadvantage. Multiple regression analyses were used to determine associations of patient, injury and geospatial characteristics with the odds of sustaining acute hand trauma and time to operative treatment., Results: Among 1,826 patients, the odds of sustaining acute hand trauma based on the ADI followed a bimodal distribution. Female sex, smoking, obesity, work-related injury and residence in a minor city were associated with increased odds, while younger age, comorbidities, and rural residence were associated with decreased odds. For 388 patients who underwent surgery within 48 hours, time to treatment was significantly increased in the highest ADI quintile, for patients who underwent fracture fixation, and for those with severe global injury severity. Multi-system injuries, moderate global injury severity and direct admission to an orthopaedic service were associated with shorter times to treatment., Conclusions: Patients in areas with greater neighborhood disadvantage may experience delayed operative care after acute hand trauma. This study highlights the importance of considering underserved populations and geospatial factors when determining the allocation of hand surgery resources., Level of Evidence: Prognostic Level III., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Background: In 2021, the United States enacted a law requiring hospitals to report prices for healthcare services. Across several healthcare services, poor compliance and wide variation in pricing was found. This study aims to investigate variation in reporting and listed prices by hospital features for high-volume hand surgeries including Carpal Tunnel release, Trigger Finger Release, De Quervain Tenosynovitis Release, and Carpometacarpal Arthroplasty., Methods: The Turquoise Health price transparency database was used to obtain listed prices and linked to hospital characteristics from the 2021 Annual American Hospital Association Survey. This study used descriptive statistics and generalized linear regression., Results: The analytic cohort included 2,652 hospitals from across the US. The highest rate of price reporting was in the Midwest (52%, n=836) and lowest in the South (39%, n=925). Compared to commercial insurers, ($3,609, 95% CI: $3,414 to $3,805) public insurance rates were significantly lower (Medicare: $1,588, 95% CI: $1,484 to $1,693, adjusted difference = -$2,021, p<0.001, Medicaid: $1,403, (95% CI: $1,194 to $1,612, adjusted difference = -$2,206, p<0.001). Listed rates for self-pay patients were not statistically different from commercial rates., Conclusions: Although pricing for high volume elective hand surgeries is frequently reported, a high proportion of hospitals do not report prices. These data highlight the need for future transparency policy to include pricing for high-volume hand surgery to give patients the ability to make financially informed choices. These results are a valuable aid for surgeons and patients to promote financially conscious decisions., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Aim: This post hoc analysis evaluated the efficacy and safety of intravenous belimumab 10 mg/kg in the South Korean subgroup of patients with systemic lupus erythematosus (SLE) enrolled in the North East Asia (NEA) study (GSK Study BEL113750; NCT01345253)., Methods: NEA was a double-blind, placebo-controlled, randomized Phase 3 trial. Patients with active, autoantibody-positive SLE were randomized 2:1 to belimumab or placebo plus standard therapy administered on Days 0, 14, and 28, and then every 28 days up to Week 48. The primary efficacy endpoint in this analysis was SLE Responder Index 4 (SRI-4) response rate at Week 52, defined as the proportion of patients achieving a ≥4-point reduction in Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score, no worsening (<0.3 increase from baseline) in Physician Global Assessment, no new British Isles Lupus Assessment Group (BILAG) A domain and <2 new BILAG B domain scores., Results: Among 100 South Korean patients enrolled in NEA, 54/66 (81.8%) belimumab- and 24/34 (70.6%) placebo-treated patients completed the double-blind phase. Significantly more belimumab- than placebo-treated patients achieved SRI-4 response at Week 52 (n = 35/66, 53.0% vs. n = 8/34, 23.5%; odds ratio [OR; 95% confidence interval (CI)]: 3.67 [1.45, 9.28]; p = .0061). The proportion of patients experiencing ≥1 adverse event was similar between groups (belimumab: n = 60/66, 90.9% vs. placebo: n = 31/34, 91.2%). No new safety signals emerged in this subgroup analysis., Conclusion: Belimumab was efficacious for the treatment of SLE and well tolerated among the South Korean subgroup of patients from the NEA study., (© 2023 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Observational research designs enable clinicians to investigate topics for which randomized-controlled trials may be difficult to conduct. However, the lack of randomization in observational studies increases the likelihood of confounders introducing bias to study results. Analytical methods such as propensity score matching and regression analysis are employed to reduce the effects of such confounding, mainly by determining characteristics of patient groups and adjusting for measured confounders. Sensitivity analyses are subsequently applied to elucidate the extent to which study results could still be affected by unmeasured confounding. The E-value is one such approach. By presenting a value that quantifies the strength of unmeasured confounding necessary to negate the observed results, the E-value is a useful heuristic concept for assessing the robustness of observational studies. This article provides an introductory overview of how the E-value can be evaluated and presented in clinical research studies., Competing Interests: Declaration of competing interest One or more of the authors (K.C.C.) receives funding from the National Institutes of Health, book royalties from Wolters Kluwer and Elsevier, and a research grant from Sonex to study carpal tunnel outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The initial approach to the treatment of desmoid tumors has changed from surgical resection to watchful waiting. However, surgery is still sometimes considered for some patients, and it is likely that a few patients would benefit from tumor removal if the likelihood of local recurrence could be predicted. However, to our knowledge, there is no tool that can provide guidance on this for clinicians at the point of care., Question/purpose: We sought to explore whether a combined molecular and clinical prognostic model for relapse in patients with desmoid tumors treated with surgery would allow us to identify patients who might do well with surgical excision., Methods: This was a retrospective, single-center study of 107 patients with desmoid tumors who were surgically treated between January 1980 and December 2015, with a median follow-up of 106 months (range 7 to 337 months). We correlated clinical variables (age, tumor size, and localization) and CTNNB1 gene mutations with recurrence-free survival. Recurrence-free survival was estimated using a Kaplan-Meier curve. Univariate and multivariable analyses of time to local recurrence were performed using Cox regression models. A final nomogram model was constructed according to the final fitted Cox model. The predictive performance of the model was evaluated using measures of calibration and discrimination: calibration plot and the Harrell C-statistic, also known as the concordance index, in which values near 0.5 represent a random prediction and values near 1 represent the best model predictions., Results: The multivariable analysis showed that S45F mutations (hazard ratio 5.25 [95% confidence interval 2.27 to 12.15]; p < 0.001) and tumor in the extremities (HR 3.15 [95% CI 1.35 to 7.33]; p = 0.008) were associated with a higher risk of local recurrence. Based on these risk factors, we created a model; we observed that patients considered to be at high risk of local recurrence as defined by having one or two factors associated with recurrence (extremity tumors and S45F mutation) had an HR of 8.4 compared with patients who had no such factors (95% CI 2.84 to 24.6; p < 0.001). From these data and based on the multivariable Cox models, we also developed a nomogram to estimate the individual risk of relapse after surgical resection. The model had a concordance index of 0.75, or moderate discrimination., Conclusion: CTNNB1 S45F mutations combined with other clinical variables are a potential prognostic biomarker associated with the risk of relapse in patients with desmoid tumors. The developed nomogram is simple to use and, if validated, could be incorporated into clinical practice to identify patients at high risk of relapse among patients opting for surgical excision and thus help clinicians and patients in decision-making. A large multicenter study is necessary to validate our model and explore its applicability., Level of Evidence: Level III, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Association of Bone and Joint Surgeons.)

Objective: Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients., Methods: We genotyped a total of 1,655 Korean patients with SLE (n = 1,243 as a discovery set and n = 412 as a replication set) using a customized genome-wide single-nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well-validated non-HLA SNPs and HLA haplotypes of SLE-risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration., Results: Childhood-onset SLE (<16 years) conferred the highest genetic risk compared with adult-onset (16-50 years) or late-onset (>50 years) SLE (P = 6.8 × 10 -6 ). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β = 0.143, P = 1.8 × 10 -6 ). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio [HR] 1.74, P = 2.2 × 10 -8 ) and anti-Sm antibody production (HR 1.85, P = 2.8 × 10 -5 ). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10 -5 ) and class V (HR 2.79, P = 1.0 × 10 -3 ), but especially lupus nephritis class V in anti-Sm-positive SLE (area under the curve 0.68, P = 1.8 × 10 -4 )., Conclusion: Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti-Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients., (© 2023 American College of Rheumatology.)

Background: Occult scaphoid fractures on initial radiographs of an injury are a diagnostic challenge to physicians. Although artificial intelligence models based on the principles of deep convolutional neural networks (CNN) offer a potential method of detection, it is unknown how such models perform in the clinical setting., Questions/purposes: (1) Does CNN-assisted image interpretation improve interobserver agreement for scaphoid fractures? (2) What is the sensitivity and specificity of image interpretation performed with and without CNN assistance (as stratified by type: normal scaphoid, occult fracture, and apparent fracture)? (3) Does CNN assistance improve time to diagnosis and physician confidence level?, Methods: This survey-based experiment presented 15 scaphoid radiographs (five normal, five apparent fractures, and five occult fractures) with and without CNN assistance to physicians in a variety of practice settings across the United States and Taiwan. Occult fractures were identified by follow-up CT scans or MRI. Participants met the following criteria: Postgraduate Year 3 or above resident physician in plastic surgery, orthopaedic surgery, or emergency medicine; hand fellows; and attending physicians. Among the 176 invited participants, 120 completed the survey and met the inclusion criteria. Of the participants, 31% (37 of 120) were fellowship-trained hand surgeons, 43% (52 of 120) were plastic surgeons, and 69% (83 of 120) were attending physicians. Most participants (73% [88 of 120]) worked in academic centers, whereas the remainder worked in large, urban private practice hospitals. Recruitment occurred between February 2022 and March 2022. Radiographs with CNN assistance were accompanied by predictions of fracture presence and gradient-weighted class activation mapping of the predicted fracture site. Sensitivity and specificity of the CNN-assisted physician diagnoses were calculated to assess diagnostic performance. We calculated interobserver agreement with the Gwet agreement coefficient (AC1). Physician diagnostic confidence was estimated using a self-assessment Likert scale, and the time to arrive at a diagnosis for each case was measured., Results: Interobserver agreement among physicians for occult scaphoid radiographs was higher with CNN assistance than without (AC1 0.42 [95% CI 0.17 to 0.68] versus 0.06 [95% CI 0.00 to 0.17], respectively). No clinically relevant differences were observed in time to arrive at a diagnosis (18 ± 12 seconds versus 30 ± 27 seconds, mean difference 12 seconds [95% CI 6 to 17]; p < 0.001) or diagnostic confidence levels (7.2 ± 1.7 seconds versus 6.2 ± 1.6 seconds; mean difference 1 second [95% CI 0.5 to 1.3]; p < 0.001) for occult fractures., Conclusion: CNN assistance improves physician diagnostic sensitivity and specificity as well as interobserver agreement for the diagnosis of occult scaphoid fractures. The differences observed in diagnostic speed and confidence is likely not clinically relevant. Despite these improvements in clinical diagnoses of scaphoid fractures with the CNN, it is unknown whether development and implementation of such models is cost effective., Level of Evidence: Level II, diagnostic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Background: Reported complication frequencies after distal radius fracture (DRF) treatment vary widely in the literature and are based mostly on observational evidence. Whether that evidence is sufficiently robust to use in practice is controversial. The E-value is an innovative sensitivity analysis that quantitates the robustness of observational evidence against unmeasured confounders, whereby a greater E-value usually implies more robust evidence and vice versa; with DRF complications, this approach can help guide readers to a more confident interpretation of the available evidence., Questions/purposes: In this study, we sought (1) to compare the complication frequencies among different DRF treatment modalities, and (2) to evaluate the robustness of these observational studies using the E-value as an index for unmeasured confounding., Methods: We searched PubMed, Embase, and SCOPUS for observational studies on the management of DRFs that were published from January 2001 to July 2021 with the last database search performed on July 31, 2021. All articles that compared different DRF treatment modalities with reported complication frequencies were included to accurately capture the quality of the observational studies in research about DRF. Risk ratios (RRs) of the overall complication and major complication risks were calculated for each subgroup comparison: volar plating versus dorsal plating, casting, external fixation, and percutaneous K-wire fixation. The RRs and their corresponding lower limits of the 95% confidence intervals (CIs) were used to derive the E-values. E-values can have a minimum possible value of 1, which signifies that the treatment-outcome association is not strong and can readily be overturned by unmeasured confounders. By contrast, a large E-value means that the observed treatment-outcome association is robust against unmeasured confounders. We averaged RRs and E-values for the effect estimates and lower limits of CIs across studies in each treatment comparison group. We identified 36 comparative observational studies that met the inclusion criteria. Seven studies compared volar with dorsal plating techniques. Volar plating was also compared with casting (eight studies), external fixation (15 studies), and percutaneous K-wire fixation (six studies)., Results: Total and major complication risks did not differ among different DRF treatments. The mean RRs for total and major complications were 1.2 (95% CI 0.4 to 3.9; p = 0.74) and 1.8 (95% CI 0.4 to 11.4; p = 0.52) for the volar versus dorsal plating group; 1.2 (95% CI 0.3 to 11.2; p = 0.87) and 1.5 (95% CI 0.3 to 14.9; p = 0.74) for the volar plating versus casting group; 0.6 (95% CI 0.2 to 2.2; p = 0.33) and 0.8 (95% CI 0.2 to 6.7; p = 0.86) for the volar plating versus external fixation group; and 0.6 (95% CI 0.2 to 2.6; p = 0.47) and 0.7 (95% CI 0.2 to 4.0; p = 0.67) for the volar plating versus K-wire fixation group. The mean E-values for total and major complication frequencies for the between-group comparison ranged from 3.1 to 5.8; these were relatively large in the context of a known complication risk factor, such as high-energy impact (RR 3.2), suggesting a reasonable level of robustness against unmeasured confounding. However, the E-values for lower limits of CIs remained close to 1, which indicates the observed complication frequencies in these studies were likely to have been influenced by unmeasured confounders., Conclusion: Complication frequencies did not differ among different DRF treatment modalities, but the observed complication frequencies from most comparative observational studies were less robust against potential unmeasured confounders. The E-value method, or another type of sensitivity analysis, should be implemented in observational hand surgery research at the individual-study level to facilitate assessment of robustness against potential unmeasured confounders., Level of Evidence: Level III, therapeutic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Multiple treatment options are available to patients with Dupuytren contracture, making shared decision-making complex. Our rigorous qualitative analysis sought to understand patient perceptions of shared decision-making in Dupuytren contracture treatment and create a conceptual framework to optimize patient-physician communication. We interviewed 30 patients with Dupuytren contracture to learn about their experience with treatment selection. The following themes were integral to shared decision-making for Dupuytren contracture treatment: discussing disease progression and treatment initiation, presenting all available treatment options, assessing patients' pre-existing biases towards treatment, patient values and preferences for treatment trade-offs, treatment risks and benefits, physician recommendation and active patient participation. This model can optimize communication about treatment options and expectations for relevant outcomes including, recovery time, contracture recurrence, complications, and treatment-related expenses. Level of evidence: V.

With the COVID-19 outbreak, emergency remote teaching - an unprepared distant mode of education became the only possible alternative for schools. The present large-scale survey with 3,672 Grade 3 and 9 students, their parents, and 863 teachers/principals was conducted in the metropolitan city of Hong Kong after half a year of school lockdown. Results showed teachers, principals, and parents were worried about students' inability to concentrate and learn without teachers' explanations. In contrast, students, particularly younger ones, were less affected. They perceived their academic achievement was not worsened and they were more lively. Generally, lack of computers and stable internet was not seen as problems. Notably, socially disadvantaged students were not different in their perceived challenges, affects, life satisfaction, or perceived academic achievement. For cities with adequate provision of computers and internet facilities, the pandemic probably forced a positive and giant leap in using advanced technologies and pedagogies., Competing Interests: Statements and declarationsCompeting Interests: The authors report there are no competing interests to declare., (© The Author(s) 2022.)

Objective  To evaluate the survival time, the failure rate and its causes, and the functional results of cemented endoprostheses, with a polyethylene body, used after resection of primary bone tumors of the distal femur. Methods  A retrospective study including 93 primary and 77 review procedures performed between 1987 and 2014. Survival was obtained by the Kaplan Meyer analysis, and the risk factors for implant failure were assessed through the Cox proportional risk model. The causes of endoprosthesis failure were classified according to Henderson et al. into five types: soft-tissue failure, aseptic loosening, structural fracture, infection, and tumor recurrence. The functional evaluation was performed using the functional classification system of the Musculoskeletal Tumor Society (MSTS) of bone sarcomas of the lower extremity, Brazilian version (MSTS-BR). Results  Osteosarcoma was the most common diagnosis; 64.5% of the patients were younger than 20 years of age; the mean follow-up was of 124.3 months. The failure rate of the primary implant was of 54.8%, and the mean survival was of 123 months. The estimated survival of the primary implant was of 63.6%, 43.5%, 24.1%, and 14.5% in 5, 10, 15, and 20 years respectively. The most common cause of failure was type 2 (37.3%). Age ≤ 26 years and right side were risk factors for failure. The mean MSTS-BR score was of 20.7 (range: 14 to 27). Conclusion The results obtained for the failure rate and survival of the implant are in accordance with those of the literature, so the procedure herein studied is adequate and yields satisfactory functional results, even in the long term., Competing Interests: Conflito de Interesses Os autores declaram não haver conflito de interesses., (Sociedade Brasileira de Ortopedia e Traumatologia. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commecial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

The increase in virtual conferences during the COVID-19 pandemic provided unexpected advantages such as increased accessibility, while also creating concern about the effectiveness of online networking and career development. Given that a variety of conference attributes are impacted by changes in conference format, we sought to investigate how plastic surgeons prioritize key aspects of conference conduct., Methods: We sent a survey based on conjoint analysis, a statistical method for evaluating consumer preferences, to active members of the American Society of Plastic Surgeons. Respondents were asked to choose between pairs of conference options, each with unique attributes. Their answers were used to calculate feature importance values and utility coefficients for the conference attributes. Subgroup analyses were conducted based on demographic factors., Results: A total of 263 respondents completed the survey. Respondents were mostly White (181 individuals [68.8%]) and men (186 [70.7%]). Nearly half (122 [46.4%]) had been practicing 20 or more years. Conference attributes with the highest feature importance values (SDs) were cost of attendance (30.4% [14.2%]) and conference format (28.8% [14.2%]). Equity initiatives (14.5% [10.1%]), reimbursement for cost (11.1% [5.7%]), and opportunities for networking (9.5% [6.0%]) had intermediate feature importance values. Environmental impact had the lowest feature importance (5.7% [3.8%])., Conclusions: Surgeons' conference preferences depend highly on format and the presence of equity initiatives, both of which can be incorporated or modified in future conferences to ensure inclusive and successful events. Meanwhile, environmental impact is less important to surgeons, suggesting a pressing need to bring sustainability issues to their attention., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

Objective: Genome-wide association studies (GWAS) have identified >100 risk loci for systemic lupus erythematosus (SLE), but the disease genes at most loci remain unclear, hampering translation of these genetic discoveries. We aimed to prioritise genes underlying the 110 SLE loci that were identified in the latest East Asian GWAS meta-analysis., Methods: We built gene expression predictive models in blood B cells, CD4 + and CD8 + T cells, monocytes, natural killer cells and peripheral blood cells of 105 Japanese individuals. We performed a transcriptome-wide association study (TWAS) using data from the latest genome-wide association meta-analysis of 208 370 East Asians and searched for candidate genes using TWAS and three data-driven computational approaches., Results: TWAS identified 171 genes for SLE (p<1.0×10 -5 ); 114 (66.7%) showed significance only in a single cell type; 127 (74.3%) were in SLE GWAS loci. TWAS identified a strong association between CD83 and SLE (p<7.7×10 -8 ). Meta-analysis of genetic associations in the existing 208 370 East Asian and additional 1498 cases and 3330 controls found a novel single-variant association at rs72836542 (OR=1.11, p=4.5×10 -9 ) around CD83 . For the 110 SLE loci, we identified 276 gene candidates, including 104 genes at recently-identified SLE novel loci. We demonstrated in vitro that putative causal variant rs61759532 exhibited an allele-specific regulatory effect on ACAP1 , and that presence of the SLE risk allele decreased ACAP1 expression., Conclusions: Cell-level TWAS in six types of immune cells complemented SLE gene discovery and guided the identification of novel genetic associations. The gene findings shed biological insights into SLE genetic associations., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Objectives: Although psychiatric disorders have been found to be associated with increased risk of dementia, previous findings are mixed, and the nature of these relationships remains poorly understood. We examined longitudinal associations between depression, anxiety, post-traumatic stress disorders (PTSD), bipolar disorder (BPD), psychotic disorders and subsequent dementia., Methods: We searched three databases for longitudinal, population-based studies investigating associations between psychiatric disorders and dementia (PROSPERO registration: CRD42020209638). We conducted narrative synthesis, and random-effects meta-analyses to obtain pooled estimates. We used meta-regression and stratified analyses to examine variation by sex, age-at-onset and follow-up time., Results: Fifty-seven citations met eligibility criteria. Most studies focussed on depression (n = 33), which was associated with subsequent all-cause dementia (pooled relative risk [RR]: 1.96, 95% confidence interval [CI]: 1.59-2.43; I 2  = 96.5%), Alzheimer's Disease (pooled RR: 1.9, 95% CI: 1.52-2.38; I 2  = 85.5%), and Vascular Dementia (pooled RR: 2.71, 95% CI: 2.48-2.97; I 2  = 0). Associations were stronger in studies with shorter follow-up periods and for severe and late-onset depression. Findings regarding anxiety were mixed, and we did not find evidence of an overall association (pooled RR: 1.18, 95% CI: 0.96-1.45; I 2  = 52.2%, n = 5). Despite sparse evidence, psychotic disorders (pooled RR: 2.19, 95% CI: 1.44-3.31; I 2  = 99%), PTSD and BPD were associated with subsequent dementia., Conclusions: People with psychiatric disorders represent high-risk groups for dementia, highlighting the importance of ongoing symptom monitoring in these groups. Findings regarding temporality and age-at-onset indicate that depression symptoms could reflect prodromal dementia for some individuals. Further longitudinal research is required to determine whether psychiatric disorders represent causal risk factors or early markers of dementia neuropathology., (© 2022 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Eccrine poroma and poroid hidradenoma are uncommon benign poroid neoplasms derived from eccrine sweat glands. There are four types of poroid neoplasms according to the position within the skin layer: hidroacanthoma simplex, eccrine poroma, dermal duct tumor, and poroid hidradenoma. Poroid neoplasms usually arise as slow-growing solitary lesions and can present different clinical presentations, such as a foot mass, an ulceration lesion, a solid cyst, a bleeding lesion or suspected melanoma. Extremities are the most common sites, especially hands and feet. However, the coexistence of these two tumors in a single lesion is extremely rare. Surgical excision represents the main treatment and can be curative, preventing malignant changes and recurrence. We describe a rare solitary tumor over the foot with clinical and histopathological features of an association of an eccrine poroma and a poroid hidradenoma that was surgically treated with no recurrence at the midterm follow-up. Level of Evidence  IV, Case Report., Competing Interests: Conflito de interesses Os autores declaram não ter conflito de interesses., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit ( https://creativecommons.org/licenses/by/4.0/ ).)

Objective: Systemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations., Methods: We newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations., Results: We identified 113 genetic regions including 46 novel loci at genome-wide significance (p<5×10 -8 ). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (r g =-0.242) and non-albumin protein (r g =0.238)., Conclusion: This study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Genome-wide association studies (GWAS) in rheumatoid arthritis (RA) have discovered over 100 RA loci, explaining patient-relevant RA pathogenesis but showing a large fraction of missing heritability. As a continuous effort, we conducted GWAS in a large Korean RA case-control population., Methods: We newly generated genome-wide variant data in two independent Korean cohorts comprising 4068 RA cases and 36 487 controls, followed by a whole-genome imputation and a meta-analysis of the disease association results in the two cohorts. By integrating publicly available omics data with the GWAS results, a series of bioinformatic analyses were conducted to prioritise the RA-risk genes in RA loci and to dissect biological mechanisms underlying disease associations., Results: We identified six new RA-risk loci ( SLAMF6 , CXCL13 , SWAP70 , NFKBIA , ZFP36L1 and LINC00158 ) with p meta <5×10 -8  and consistent disease effect sizes in the two cohorts. A total of 122 genes were prioritised from the 6 novel and 13 replicated RA loci based on physical distance, regulatory variants and chromatin interaction. Bioinformatics analyses highlighted potentially RA-relevant tissues (including immune tissues, lung and small intestine) with tissue-specific expression of RA-associated genes and suggested the immune-related gene sets (such as CD40 pathway, IL-21-mediated pathway and citrullination) and the risk-allele sharing with other diseases., Conclusion: This study identified six new RA-associated loci that contributed to better understanding of the genetic aetiology and biology in RA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Schwannoma is a benign neural sheath tumor of the soft tissue, and its intraosseous presentation is very rare. It is estimated that intraosseous schwannomas represent 0.2% of all bone tumors. The tumor may affect any site of the skeleton, including the mandible, the sacrum, vertebral bodies, the ulna, the humerus, the femur, the tibia, the patella, the scapula, the ribs, and small bones of the hand. The involvement of the calcaneus has only been reported four times in the literature. The present study reports the case of a 49-year-old male with right hindfoot pain and a radiological finding of an osteolytic bone lesion in the calcaneus. The diagnosis was confirmed by histopathological study. The treatment of choice was an intralesional resection with adjuvant local control, and bone defect substitution with polymethylmethacrylate and fixation with two cannulated screws. The patient had a satisfactory postoperative evolution; after 1 year, he is asymptomatic, with good functional response and no evidence of disease. The present case report shows the clinical, radiological, and pathological features of a rare benign bone neoplasm. Moreover, intraosseous schwannoma should be included in the differential diagnosis of osteolytic calcaneal lesions., Competing Interests: Conflitos de Interesses Os autores declaram não haver conflitos de interesses.

Bioaerosol generated in wastewater treatment plants has potential to harm human health. Survival of bacteria in bioaerosol during suspension is one of the major factors that affect its biological risk. It is hypothesized that bacteria grown in different wastewater have different physiology and lead to variation in airborne survival. This study investigated the relationship between the cultured conditions and the bioaerosol survival. Synthetic wastewater was used as the culture medium to simulate the water quality of wastewater. Escherichia coli BW25113 were cultured in different conditions, including growth salinity, growth temperature, growth pH, and presence of pesticide. The fatty acid composition and the reduction in airborne survival of the E. coli cultured under these conditions were determined and compared. Results showed that increasing growth salinity and temperature led to a lower reduction in airborne survival of E. coli. E. coli cultured at pH 6 had a higher reduction in airborne survival than those cultured at pH 7 and 8. Moreover, a correlation was observed between the membrane fluidity (fluidity index) and the reduction airborne survival for both aerosolization and airborne suspension. A link between culture conditions, bacterial membrane fluidity, and airborne survival was established. Culture conditions (wastewater quality) that lead to a low membrane fluidity of bacteria increase the airborne survival of bioaerosol, and vice versa. This provides a new aspect to evaluate bioaerosol survival and improve assessment on biological risk of bioaerosols.

Biofilm formation by Klebsiella pneumoniae on indwelling medical devices increases the risk of infection. Both type 1 and type 3 fimbriae are important factors in biofilm formation by K. pneumoniae . We found that a putative enzyme II (EII) complex of the phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS), etcA (EIIA)- etcB (EIIB)- etcC (EIIC), regulated biofilm and type 3 fimbriae formation by K. pneumoniae STU1. In this study, the regulatory mechanism of etcABC in K. pneumoniae type 3 fimbriae formation was investigated. We found via quantitative RT-PCR that overexpression of etcABC enhanced the transcription level of the mrk operon, which is involved in type 3 fimbriae synthesis, and reduced the transcription level of the fim operon, which is involved in type 1 fimbriae synthesis. To gain further insight into the role of etcABC in type 3 fimbriae synthesis, we analyzed the region upstream of the mrk operon and found the potential cyclic 3'5'-adenosine monophosphate (cAMP) receptor protein (CRP) binding site. After crp was deleted in K. pneumoniae STU1 and two clinical isolates, these three crp mutant strains could not express MrkA, the major subunit of the fimbrial shaft, indicating that CRP positively regulated type 3 fimbriae synthesis. Moreover, a crp mutant overexpressing etcABC could not express MrkA, indicating that the regulation of type 3 fimbriae by etcABC was dependent on CRP. In addition, deletion of cyaA , which encodes the adenylyl cyclase that synthesizes cAMP, and deletion of crr , which encodes the glucose-specific EIIA, led to a reduction in lac operon regulation and therefore bacterial lactose uptake in K. pneumoniae . Exogenous cAMP but not etcABC overexpression compensated for the role of cyaA in bacterial lactose uptake. However, either etcABC overexpression or exogenous cAMP compensated for the role of crr in bacterial lac operon regulation that would eventually restore lactose uptake. We also found via ELISA and the luxCDABE reporter system that overexpression of etcABC increased intracellular cAMP levels and the transcription level of crp , respectively, in K. pneumoniae . In conclusion, overexpression of etcABC positively regulated cAMP production and cAMP-CRP activity to activate the mrk operon, resulting in increased type 3 fimbriae synthesis in K. pneumoniae .

Systemic lupus erythematosus (SLE) is a multi-systemic chronic autoimmune disease, the etiology of SLE is still unclear. Only a few studies evaluated the associations between air pollution and SLE. We conducted a population-based cohort study in Taiwan to examine the associations of air pollution with SLE. A total of 682,208 individuals aged 18-70 years were retrieved from National Health Insurance Research Database. We applied 1-km resolution land use regression and satellite-based models to estimate air pollutant concentrations during 2001-2010. The mixed effect Cox models with time-dependent variables were performed to estimate the associations between air pollution and SLE, as hazard ratios (HRs) with 95% confidence interval (CI). We identified 1292 newly diagnosed SLE patients with average age of 43.26 ± 13.64 years, most of them were female. There were positive associations of SLE with exposure to a 9.76 ppb increase in nitrogen dioxide (NO 2 ), a 0.20 ppm increase in carbon monoxide (CO), and a 10.2 μg/m 3 increase in fine particles (PM 2.5 ) (HR = 1.21, 95% CI: 1.08-1.36, HR = 1.44, 95% CI: 1.31-1.59, and HR = 1.12, 95% CI: 1.02-1.23, respectively). Additionally, we observed negative associations with ozone (O 3 ) and sulfur dioxide (SO 2 ). According to the exposure-response relationships, exposure to NO 2 between 28 and 38 ppb, exposure to CO above 0.6 ppm, and exposure to PM 2.5 between 18 and 46 μg/m 3 were positively associated with SLE. The results suggested that long-term exposure to traffic-related gaseous air pollutants (NO 2 and CO) less than current National Ambient Air Quality Standards and PM 2.5 are significantly associated with the risk of SLE., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We describe a case of Streptococcus lutetiensis infective endocarditis occurring in a patient following colonic polypectomy. The patient had multiple risk factors for infective endocarditis including pre-existing mitral valve prolapse and regurgitation. Transoesophageal echocardiography revealed a friable mass on the posterior mitral valve leaflet, confirming the diagnosis. The patient was treated with intravenous antibiotics, successfully underwent mitral valve surgery and was discharged home for outpatient follow-up. This report details an uncommon case presentation, highlights areas for improvement in clinical practice, and summarises the current knowledge available in the literature regarding Streptococcus bovis infective endocarditis., Learning Points: Infective endocarditis occurring in association with gastrointestinal endoscopy is rare.Clinical suspicion of infective endocarditis after colonic polypectomy or biopsy should be maintained, especially in those with risk factors for infective endocarditis.Antibiotic prophylaxis against infective endocarditis is not recommended for routine gastrointestinal endoscopic procedures., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests.

Aim: Despite high clinical disease activity, some patients with active rheumatoid arthritis (RA) have normal acute phase reactant (APR) values. This study aimed to determine the clinical outcomes of active RA patients with normal APR values., Method: Of 5376 patients with RA enrolled in the Korean observational study network for arthritis (KORONA) registry, 400 patients with disease duration of <2 years who had Clinical Disease Activity Index (CDAI) score of >2.8 at baseline, biologic-naïve, and erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) drawn at both baseline and 2-year follow-up visits were identified. Patients were grouped according to baseline APR levels: normal APRs, one APR elevated, and both APRs elevated., Results: Baseline tender and swollen joint counts, mean CDAI and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores were significantly lower in the normal APRs group compared with APR-elevated groups (P < 0.0001). At 2-year follow-up, mean CDAI scores, HAQ-DI, and percentage of the patient achieving remission were not significantly different between the normal APRs group compared with the APR-elevated groups regardless of the baseline disease activity. However, in patients with baseline CDAI moderate to high disease activity, the normal APRs group less frequently required initiation of the biologic disease-modifying anti-rheumatic drugs compared with the APR-elevated groups (P = 0.044)., Conclusion: Active RA patients with normal APR values have milder disease presentation, but similar clinical outcomes to those with elevated APRs., (© 2019 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Classical alleles, SNPs, and amino-acid residues of eight HLA genes were imputed across 4,915 SLE cases and 13,513 controls from Eastern Asia. We performed association followed by conditional analysis across HLA, assessing both overall SLE risk and risk of autoantibody production. DR15 alleles HLA-DRB1*15:01 (P = 1.4x10-27, odds ratio (OR) = 1.57) and HLA-DQB1*06:02 (P = 7.4x10-23, OR = 1.55) formed the most significant haplotype (OR = 2.33). Conditioned protein-residue signals were stronger than allele signals and mapped predominantly to HLA-DRB1 residue 13 (P = 2.2x10-75) and its proxy position 11 (P = 1.1x10-67), followed by HLA-DRB1-37 (P = 4.5x10-24). After conditioning on HLA-DRB1, novel associations at HLA-A-70 (P = 1.4x10-8), HLA-DPB1-35 (P = 9.0x10-16), HLA-DQB1-37 (P = 2.7x10-14), and HLA-B-9 (P = 6.5x10-15) emerged. Together, these seven residues increased the proportion of explained heritability due to HLA to 2.6%. Risk residues for both overall disease and hallmark autoantibodies (i.e., nRNP: DRB1-11, P = 2.0x10-14; DRB1-13, P = 2.9x10-13; DRB1-30, P = 3.9x10-14) localized to the peptide-binding groove of HLA-DRB1. Enrichment for specific amino-acid characteristics in the peptide-binding groove correlated with overall SLE risk and with autoantibody presence. Risk residues were in primarily negatively charged side-chains, in contrast with rheumatoid arthritis. We identified novel SLE signals in HLA Class I loci (HLA-A, HLA-B), and localized primary Class II signals to five residues in HLA-DRB1, HLA-DPB1, and HLA-DQB1. These findings provide insights about the mechanisms by which the risk residues interact with each other to produce autoantibodies and are involved in SLE pathophysiology., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Recent studies have shown that a combination treatment of mycophenolate mofetil (MMF) and tacrolimus (TAC) may be an option for lupus nephritis (LN) patients that do not adequately respond to initial treatment. We evaluated the efficacy and safety of the combination treatment of MMF and TAC in LN patients with suboptimal response to prior MMF or TAC treatments., Methods: In this multicentre study, we retrospectively enrolled 62 patients with class III, IV, or V LN who inadequately responded to MMF or TAC treatment. Those patients were then treated with a combination of MMF and TAC for 6 months. The primary outcome was complete remission (CR) at 6 months, and secondary outcomes included overall response and adverse events., Results: After 6 months of treatment with the drug combination, CR was achieved in 14 of 62 patients (22.6%), and 35 (56.5%) patients responded. A significant reduction in proteinuria and lupus disease activity score was observable after 3 months. After 1 year, the CR rate increased to 36.4% (20 of 55 patients), and the overall response rate (n=38, 69.1%) also increased from 6 months. Twenty-one patients reported 29 adverse events, including severe infection requiring hospitalisation (n=3, 10.3%), infection not requiring hospitalisation (n=2, 6.9%), and herpes zoster (n=4, 13.8%)., Conclusions: Our findings suggest that a combined MMF and TAC treatment, with a favourable adverse-event profile, may be a beneficial option for LN patients with inadequate response to either MMF or TAC treatments.

Rationale: Dystrophic calcinosis occurs in chronically damaged tissue in patients with complicated autoimmune diseases. The therapeutic options are limited, and the treatment response rate is variable. Here, we describe a rare case of dystrophic calcinosis treated with leflunomide in a patient with overlap syndrome., Patient Concerns: A 53-year-old woman who was diagnosed with overlaps syndrome (systemic sclerosis [SSc] with rheumatoid arthritis [RA]), presented to our hospital with pain and swelling in both wrists, and underwent radiography, bone scan, and biopsy examination., Diagnoses: This patient was diagnosed with dystrophic calcinosis in overlaps syndrome., Interventions: The conventional disease-modifying drugs were not effective. Hence, leflunomide was administered., Outcomes: Simple radiography and bone scan showed resolved mass-like dystrophic calcinosis on both wrists of the patient after the use of leflunomide., Lessons: The control of underlying disease is important in the treatment of dystrophic calcinosis. The use of leflunomide maybe an option in treatment of dystrophic calcinosis combined with RA.

Free fatty acids (FFAs) are considered the principal inducers of lipotoxicity, leading to cell dysfunction and/or cell death. Lipotoxicity in Schwann cells (SCs) damages neurons, which may be associated with peripheral neuropathies and axon degeneration. However, the molecular mechanism by which FFAs exert lipotoxicity in SCs remains to be established. In the present study, we demonstrate that palmitate exerts lipotoxicity in SCs through apoptosis and that palmitate-induced lipotoxicity in SCs is mediated through reactive oxygen species (ROS) generation. We observed that the six-transmembrane protein of prostate 2 (STAMP2), which plays a pivotal role in lipid homeostasis, is expressed in SCs. We further demonstrate that palmitate induces lipoapoptosis in SCs through ROS generation-mediated STAMP2 downregulation and that STAMP2 depletion accelerates the palmitate-exerted lipoapoptosis in SCs, indicating that STAMP2 confers on SCs the ability to resist palmitate-induced lipotoxicity. In conclusion, palmitate induces lipoapoptosis in SCs through ROS generation-mediated STAMP2 downregulation. Our findings indicate that ROS and STAMP2 may represent suitable targets for pharmacological interventions targeting lipotoxicity-associated peripheral neuropathies and axon degeneration., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: Platelet rich plasma (PRP) is rich in growth factors and has been shown to improve healing in a variety of wounds. We determined the effects of PRP on healing and scarring in full thickness porcine burns with and without tangential excision and grafting (TEG)., Methods: Standardized full thickness 5cm by 5cm burns were created on each of the backs and flanks of 10 anesthetized female pigs (25kg) using a validated model. The burns were created with a heating device that emits heat at a temperature of 400°C for a period of 30s. The burns were randomized to one of six treatments: no TEG or PRP, no TEG+PRP, early (day 2) TEG and no PRP, early TEG+PRP, late (day 14) TEG and no PRP, and late TEG+PRP. Tangential excision was performed down to viable tissue and autografts were 0.2mm thick. When used, a thin layer of autologous PRP was applied below the graft. All wounds were then treated with a topical antibiotic ointment 3 times weekly for 42 days. Digital images and full thickness biopsies were taken at 9, 11, 14, 18, 21, 28, 35 and 42days after injury to determine percentage reepithelialization, scar depth, and scar contraction. Tissue sections were stained with H&E and viewed by a dermatopathologist masked to treatment assignment., Results: There was no reduction in platelet and white blood cell concentrations in PRP and blood samples for the first 14days after-full thickness burns. A total of 120 burns were created on 10 animals evenly distributed between the six treatment groups. Burns undergoing early TEG reepithelialized fastest and with the thinnest scars followed by late TEG. Burns that did not undergo TEG had the slowest reepithelialization and greatest amount of scarring. Application of PRP had no additional effects on reepithelialization, scar depth, or scar contraction in any of the treatment groups., Conclusions: Addition of PRP had similar effects on reepithelialization and scarring of full thickness porcine burns as standard topical antibiotic ointment regardless of whether the burns underwent excision or grafting or the timing of excision and grafting., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)

Free fatty acids (FFAs), which are elevated with metabolic syndrome, are considered the principal offender exerting lipotoxicity. Few previous studies have reported a causal relationship between FFAs and osteoarthritis pathogenesis. However, the molecular mechanism by which FFAs exert lipotoxicity and induce osteoarthritis remains largely unknown. We here observed that oleate at the usual clinical range does not exert lipotoxicity while oleate at high pathological ranges exerted lipotoxicity through apoptosis in articular chondrocytes. By investigating the differential effect of oleate at toxic and nontoxic concentrations, we revealed that lipid droplet (LD) accumulation confers articular chondrocytes, the resistance to lipotoxicity. Using high fat diet-induced osteoarthritis models and articular chondrocytes treated with oleate alone or oleate plus palmitate, we demonstrated that articular chondrocytes gain resistance to lipotoxicity through protein kinase casein kinase 2 (PKCK2)-six-transmembrane protein of prostate 2 (STAMP2)-and fat-specific protein 27 (FSP27)-mediated LD accumulation. We further observed that the exertion of FFAs-induced lipotoxicity was correlated with the increased concentration of cellular FFAs freed from LDs, whether FFAs are saturated or not. In conclusion, PKCK2/STAMP2/FSP27-mediated sequestration of FFAs in LD rescues osteoarthritic chondrocytes. PKCK2/STAMP2/FSP27 should be considered for interventions against metabolic OA., Competing Interests: The authors declare that they have no conflict of interest.

Objectives: There are no well accepted animal models of chronic wounds, limiting advances in understanding and treatment of chronic ulcers. We developed a porcine wound model which combines multiple factors involved in chronic wounds to create a contaminated necrotic eschar and evaluated the debriding efficacy of a novel bromelain based enzymatic debriding agent (EscharEx)., Methods: Contaminated ischemic wounds were created on the flanks of domestic pigs by 'sandwiching' the skin between 2 'O' rings (1 placed on the surface of the skin and the other underneath the skin) for 24h prior to dermatomal excision of the necrotic eschar and its contamination with Staphylococcus aureus and Candida albicans. After confirming the development of infected eschars, additional animals were used to compare the effects of daily application of topical EscharEx or its hydrating vehicle on eschar debridement as a control., Results: In all cases, application of the 'O' rings resulted in full thickness necrotic ecshars with invasive infections, which did not reepithelialize and sloughed off spontaneously within 14-21 days. All wounds reepithelialized within 28-42 days forming contracted scars. All EscharEx treated eschars were completely debrided within 7-9 days, while no debridement was evident in eschars treated with the control gel., Conclusions: Our model simulates the initial phase of chronic wounds characterized by a contaminated necrotic eschar allowing evaluation of wound debriding agents, and that a bromelain-based debriding agent completely debrides the contaminated necrotic eschars within one week in this model., (Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.)

Background/aims: For patients with ankylosing spondylitis (AS), golimumab has consistent efficacy in controlling disease activity over 5 years but its benefit in preventing radiographic progression was less clear at 4 years. To predict radiographic progression, we analyzed the baseline characteristics of AS patients in a Korean population., Methods: Sixty-eight Korean patients with AS participated in the phase 3, multicenter, randomized, placebo-controlled, double-blind trial (GO-RAISE) which has previously been described. Baseline modified stoke AS spine score (mSASSS) and change in mSASSS from baseline (ΔmSASSS) until week 208 were analyzed in the Korean patients enrolled in the GO-RAISE study., Results: Although Korean patients had lower baseline mSASSS compared to non-Korean patients and received active management, radiographic progression was not prevented. Korean patients who did not undergo radiographic progression of spinal lesions of AS were younger and had shorter symptomatic duration, lower Bath AS functional and metrology indices, better chest expansion, and lower baseline mSASSS. The baseline mSASSS and ΔmSASSS were positively correlated in Korean AS patients ( p < 0.001). Radiographic progression was more prevalent (80.0%) when baseline mSASSS > 10 and less common (13.0%) with baseline mSASSS = 0., Conclusions: In Korean AS patients, radiographic progression of the spine after 4 years was predicted effectively by the initial severity of the spinal lesion(s) in patients treated with golimumab.

Aim: To determine characteristics of rheumatoid arthritis (RA) patients in Korea using disease-modifying anti-rheumatic drugs (DMARDs) for at least 6 months, and to identify factors associated with poor health-related outcomes., Method: A total of 2000 RA patients aged > 20 years, treated with DMARDs for at least 6 months, and signed informed consent, were enrolled in this non-interventional, multicenter, cross-sectional observational study from December 2012 to June 2013. Health-related quality of life (HRQoL) was measured using EuroQuol 5D (EQ-5D) and functional disability was measured using the Korean Health Assessment Questionnaire (KHAQ). Univariate and multivariate linear regression analyses were used to determine the association between patient characteristics and patient-reported outcomes (PROs)., Results: Of all RA patients, 84% were female, patients with low Disease Activity Score of 28 joints erythrocyte sedimentation rate (DAS-28-ESR < 3.2) was 54%, while moderate (DAS-28-ESR 3.2-5.1) and high disease activity score (DAS-28-ESR > 5.1) were 38% and 7.6%, respectively. Mean EQ-5D index score and KHAQ score were 0.6 ± 0.28 and 0.7 ± 0.67, respectively. In multivariate analysis with both PROs, average HRQoL and functional disability score appeared to be worse in persons with older age compared to younger age (P < 0.001), and worse in females compared to males (P < 0.001). Compared to patients having lower DAS (< 3.2), those with moderate and highest DAS (3.2-5.1 and > 5.1) had worse outcome measures (P < 0.001)., Conclusion: In this study, higher DAS was one of the most influential factors for poor PROs among all other factors. Therefore, we could suggest appropriate treatment approaches according to DAS along with other significantly associated factors with PROs in the early stage of RA., (© 2016 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background/purpose: Klebsiella pneumoniae is one of the leading causes of device-related infections (DRIs), which are associated with attachment of bacteria to these devices to form a biofilm. The latter is composed of not only bacteria but also extracellular polymeric substances (EPSes) consisting of extracellular DNAs, polysaccharides, and other macromolecules. The phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS) regulates diverse processes of bacterial physiology. In the genome of K. pneumoniae MGH 78578, we found an uncharacterized enzyme II complex homolog of PTS: KPN00353 (EIIA homolog), KPN00352 (EIIB homolog), and KPN00351 (EIIC homolog). The aim of this study was to characterize the potential physiological role of KPN00353, KPN00352, and KPN00351 in biofilm formation by K. pneumoniae., Methods/results: We constructed the PTS mutants and recombinant strains carrying the gene(s) of PTS. The recombinant K. pneumoniae strain overexpressing KPN00353-KPN00352-KPN00351 produced more extracellular matrix than did the vector control according to transmission and scanning electron microscopy. Judging by quantification of biofilm formation, of extracellular DNA (eDNA), and of capsular polysaccharide, the recombinant strain overexpressing KPN00353-KPN00352-KPN00351 produced more biofilm and capsular polysaccharide after overnight culture and more eDNA in the log phase as compared to the vector control., Conclusion: The genes, KPN00353-KPN00352-KPN00351, encode a putative enzyme II complex in PTS and positively regulate biofilm formation by enhancing production of eDNA and capsular polysaccharide in K. pneumoniae. Five proteins related to chaperones, to the citric acid cycle, and to quorum sensing are upregulated by the KPN00353-KPN00352-KPN00351 system., (Copyright © 2017. Published by Elsevier B.V.)

1,3-Propanediol (1,3-PD) is a valuable chemical intermediate in the synthesis of polyesters, polyethers, and polyurethanes, which have applications in various products such as cloth, bottles, films, tarpaulins, canoes, foam seals, high-resilience foam seating, and surface coatings. Klebsiella pneumoniae can produce 1,3-PD from glycerol. In this study, KPN00353, an EIIA homologue in the phosphoenolpyruvate (PEP):carbohydrate phosphotransferase system (PTS), was found to play a negative regulatory role in 1,3-PD production under microaerobic conditions via binding to glycerol kinase (GlpK). The primary sequence of KPN00353 is similar to those of the fructose-mannitol EIIA (EII Fru and EIIA Mtl ) family. The interaction between KPN00353 and GlpK resulted in inhibition of the synthesis of glycerol-3-phosphate (G3P) and correlated with reductions in glycerol uptake and the production of 1,3-PD. Based on structure modeling, we conclude that residue H65 of KPN00353 plays an important role in the interaction with GlpK. We mutated this histidine residue to aspartate, glutamate, arginine and glutamine to assess the effects of each KPN00353 variant on the interaction with GlpK, on the synthesis of G3P and on the production of 1,3-PD. Our results illuminate the role of KPN00353 in 1,3-PD production by K. pneumoniae under microaerobic conditions.

To identify the prevalence of interstitial lung disease (ILD) in Korean patients with rheumatoid arthritis (RA) and assess its effect on mortality. A total of 3555 patients with RA, with chest X-ray or chest computed tomography (CT) data at enrollment were extracted from the KORean Observational study Network for Arthritis cohort, a nationwide prospective cohort for patients with RA in Korea. The patients were classified into two groups: (1) an ILD group by chest X-ray or chest CT scan, and (2) a non-ILD group by these modalities. After comparing the characteristics of the groups at enrollment, mortalities were compared using the log-rank test. To explore the impact of ILD on mortality, Cox proportional hazard models were used. Sixty-four patients (1.8%) were identified with ILD. Male and older patients were more common in the ILD group. During a mean follow-up of 24 months, 6 patients (9.4%) in the ILD group and 25 patients (0.7%) in the non-ILD group died; the survival rate was significantly worse in the ILD group (p < 0.01). On adjusted analysis, ILD was significantly associated with increased mortality (HR 7.89, CI 3.16-19.69, p < 0.01); the risk of death in patients with ILD was even higher than in patients with cardiovascular disease (CVD, HR 4.10, CI 1.79-9.37, p < 0.01). The prevalence of ILD was 1.8% in Korean patients with RA. ILD is a major risk factor for mortality in patients with RA.