Vertebral Body Reshaping after Fractures: An Important Index of Recovery in Glucocorticoid-Treated Children.

PURPOSE: In this 6-year study we identified factors associated with spontaneous vertebral body reshaping in glucocorticoid (GC)-treated children with leukemia, rheumatic disorders, and nephrotic syndrome. METHODS: Subjects were 79 children (mean age 7.4 years) who had vertebral fracture (VF) evaluation on lateral spine radiographs at least 1 year after VF detection. VF were graded using the modified Genant semiquantitative method and fracture burden for individuals was quantified using the spinal deformity index (SDI; sum of grades from T4 to L4). RESULTS: Sixty-five children (82.3%) underwent complete vertebral body reshaping (median time from VF detection to complete reshaping 1.3 years by Cox proportional hazard modeling). Of 237 VF, the majority (83.1%) ultimately reshaped, with 87.2% reshaping in the thoracic region vs 70.7% in the lumbar region (P = .004). Cox models showed that (1) every g/m2 increase in GC exposure in the first year after VF detection was associated with a 19% decline in the probability of reshaping; (2) each unit increase in the SDI at the time of VF detection was associated with a 19% decline in the probability of reshaping [hazard ratio (HR) = 0.81; 95% confidence interval (CI) = 0.71, 0.92; P = .001]; (3) each additional VF present at the time of VF detection reduced reshaping by 25% (HR = 0.75; 95% CI = 0.62, 0.90; P = .002); and (4) each higher grade of VF severity decreased reshaping by 65% (HR = 0.35; 95% CI = 0.21, 0.57; P < .001). CONCLUSION: After experiencing a VF, children with higher GC exposure, higher SDI, more severe fractures, or lumbar VF were at increased risk for persistent vertebral deformity.

Prevalence, Incidence, and Predictors of Self-reported Swallowing Difficulties in Community-Dwelling Adults: A Population-Based Study from the Canadian Longitudinal Study on Aging (CLSA).

There is a paucity of evidence from population-based studies identifying prevalence and incidence of dysphagia, as well as health and sociodemographic risk factors that may contribute to its development. As such, the current study aimed to determine prevalence, incidence, and associated predictors of dysphagia in adults. The Canadian Longitudinal Study on Aging is a nationally representative population study that follows 51,338 Canadians over 45 years of age. Biological, medical, psychological, social, lifestyle and economic data are collected. A secondary analysis of the data was conducted to determine prevalence, incidence, and the predictors of self-reported swallowing difficulty in adults between 45 and 85 years of age. Rates of swallowing difficulty by demographic risk factor, as well as lifestyle and health factors were analyzed using descriptive statistics. Associations between lifestyle and health variables with dysphagia were tested using Chi-square tests or t tests, as appropriate. Logistic regression was used to determine the predictors of self-reported swallowing difficulties. Overall prevalence of self-reported swallowing difficulties in adults over the age of 45 was 10.6% and increased to 13.7% after 3 years. Significant differences (p < 0.001) in self-reported swallowing difficulty at baseline were apparent across smoking status, requiring help to prepare meals, life satisfaction, social participation, all disease categories except dementia, number of medications, cognition, oral health status, and frailty. Incidence of dysphagia was 8.6%. Regression analyses suggested the following independent predictors of reports of swallowing difficulty: older age; non-white ethnicity; female sex; poor oral health; malnutrition; and frailty. These predictors should be carefully considered to ensure we are screening at-risk populations. Social determinants of health, such as ethnicity, must also be considered to ensure equitable care across the population.

AhR regulates VEGF expression by promoting STAT1 transcriptional activity, thereby affecting endothelial angiogenesis in acute limb ischemia.

BACKGROUND: Angiogenesis has great potential in the treatment of acute limb ischemia (ALI). Here, we aimed to investigate the effect and mechanism of Aryl hydrocarbon receptor (AhR) on angiogenesis in ALI. METHODS: The ALI mouse model was constructed by femoral artery ligation, and the cell ischemia injury was induced by Hypoxia/serum deprivation. The laser doppler perfusion imaging was executed to detect the limb blood flow velocity. The tube formation assay was performed to evaluate angiogenesis. The cell viability was measured by 3-(45)-dimethylthiahiazo(-z-y1)-35-di-phenytetrazoliumromide. The cell migration was detected by wound healing assay. Hematoxylin-eosin, immunohistochemistry, immunofluorescence, dual-luciferase reporter gene assay, and Chromatin immunoprecipitation assay were conducted. RESULTS: In ALI models, AhR expression was increased and translocated from cytoplasm to nucleus. Besides, necrosis and inflammatory infiltration were also increased in gastrocnemius tissues of model mice. In addition, AhR loss (LV-sh-AhR) promoted cell viability, angiogenesis, and migration, and also elevated the levels of vascular endothelial growth factor (VEGF), Tie2, and Ang2 in HUVEC models with Hypoxia/serum deprivation injury. Meanwhile, the interaction between AhR and signal transducer and activator of transcription 1 (STAT1), as well as STAT1 and VEGF, has also been confirmed. Co-transfection of LV-sh-AhR and LV-STAT1 suppressed cell viability, angiogenesis, and migration of injured HUVECs. Furthermore, injection of AAV2/9-shAhR in vivo also promoted angiogenesis, which was consistent with the in vitro experimental results. CONCLUSIONS: In ALI models, activated AhR was translocated to the nucleus and down-regulated VEGF expression by promoting the transcriptional activity of STAT1, thereby inhibiting endothelial angiogenesis.

The correlation between multiple congenital anomalies hypotonia seizures syndrome 2 and PIGA: a case of novel PIGA germline variant and literature review.

BACKGROUND: PIGA (PIG class A) gene codes for the PIG-A protein, which is a catalytic subunit of GPI-GlcNAc transferase. GPI-anchored proteins play an important role in the metabolism of mammals. Somatic variants of PIGA genes in bone marrow hematopoietic stem cells often result in paroxysmal nocturnal haemoglobinuria, and the germline PIGA variants cause multiple congenital anomalies hypotonia seizures syndrome 2 (MCAHS2) because of glycosylphosphatidylinositol metabolic abnormalities. METHODS: Whole exome sequencing was performed on peripheral blood sample of the patient with MCAHS2. A novel germline PIGA variant was found, and Sanger sequencing was performed as verification for the variant. After that, we used the keywords to retrieve relevant reports and provided a literature review. RESULTS: A novel hemizygous germline PIGA variant (NM_002641.3:c.971G > A) at exon4 was identified through whole exome sequencing. And it was a highly probable pathogenic variant. Sanger sequencing yielded consistent results. The missense variant cause change of p.(Cys324Tyr) in the transcription product according to the predicted outcomes. CONCLUSION: We reported a case of MCAHS2 caused by a novel PIGA variant. Following a review of the literature, we suggested that MCAHS2 should be considered as a disorder spectrum consisting of core symptoms, multi-system impairment, and premature death. The core symptoms include hypotonia, psychomotor delay, epilepsy (intractable epilepsy mostly) and early death. Core symptoms nearly happened to almost all patients. Meanwhile, MCAHS2 involves a wide range of organ and system impairments with changeable form.

Extracellular Vesicles from BMSCs Prevent Glucocorticoid-Induced BMECs Injury by Regulating Autophagy via the PI3K/Akt/mTOR Pathway.

Osteonecrosis of the femoral head (ONFH) is a common clinical disease with a high disability rate. Injury of bone microvascular endothelial cells (BMECs) caused by glucocorticoid administration is one of the important causes of ONFH, and there is currently a lack of effective clinical treatments. Extracellular vesicles derived from bone stem cells (BMSC-EVs) can prevent ONFH by promoting angiogenesis and can inhibit cell apoptosis by regulating autophagy via the PI3K/Akt/mTOR signaling pathway. The present study aimed to investigate the effect of extracellular vesicles derived from bone marrow stem cells (BMSC) on a glucocorticoid-induced injury of BMECs and possible mechanisms. We found that BMSC-EVs attenuated glucocorticoid-induced viability, angiogenesis capacity injury, and the apoptosis of BMECs. BMSC-EVs increased the LC3 level, but decreased p62 (an autophagy protein receptor) expression, suggesting that BMSC-Exos activated autophagy in glucocorticoid-treated BMECs. The protective effects of BMSC-EVs on the glucocorticoid-induced injury of BMECs was mimicked by a known stimulator of autophagy (rapamycin) and could be enhanced by co-treatment with an autophagy inhibitor (LY294002). BMSC-EVs also suppressed the PI3K/Akt/mTOR signaling pathway, which regulates cell autophagy, in glucocorticoid-treated BMECs. In conclusion, the results indicate that BMSC-EVs prevent the glucocorticoid-induced injury of BMECs by regulating autophagy via the PI3K/Akt/mTOR pathway.

Associations between lung function and physical and cognitive health in the Canadian Longitudinal Study on Aging (CLSA): A cross-sectional study from a multicenter national cohort.

BACKGROUND: Low lung function is associated with high mortality and adverse cardiopulmonary outcomes. Less is known of its association with broader health indices such as self-reported respiratory symptoms, perceived general health, and cognitive and physical performance. The present study seeks to address the association between forced expiratory volume in 1 second (FEV1), an indicator of lung function, with broad markers of general health, relevant to aging trajectory in the general population. METHODS AND FINDINGS: From the Canadian general population, 22,822 adults (58% females, mean age 58.8 years [standard deviation (SD) 9.6]) were enrolled from the community between June 2012 and April 2015 from 11 Canadian cities and 7 provinces. Mixed effects regression was used to assess the cross-sectional relationship between FEV1 with self-reported respiratory symptoms, perceived poor general health, and cognitive and physical performance. All associations were adjusted for age, sex, body mass index (BMI), education, smoking status, and self-reported comorbidities and expressed as adjusted odds ratios (aORs). Based on the Global Lung Function Initiative (GLI) reference values, 38% (n = 8,626) had normal FEV1 (z-scores >0), 37% (n = 8,514) mild (z-score 0 to > -1 SD), 19% (n = 4,353) moderate (z-score -1 to > -2 SD), and 6% (n = 1,329) severely low FEV1 (z-score = < -2 SD). There was a graded association between lower FEV1 with higher aOR [95% CI] of self-reported moderate to severe respiratory symptoms (mild FEV1 1.09 [0.99 to 1.20] p = 0.08, moderate 1.45 [1.28 to 1.63] p < 0.001, and severe 2.67 [2.21 to 3.23] p < 0.001]), perceived poor health (mild 1.07 [0.9 to 1.27] p = 0.45, moderate 1.48 [1.24 to 1.78] p = <0.001, and severe 1.82 [1.42 to 2.33] p < 0.001]), and impaired cognitive performance (mild 1.03 [0.95 to 1.12] p = 0.41, moderate 1.16 [1.04 to 1.28] p < 0.001, and severe 1.40 [1.19 to 1.64] p < 0.001]). Similar graded association was observed between lower FEV1 with lower physical performance on gait speed, Timed Up and Go (TUG) test, standing balance, and handgrip strength. These associations were consistent across different strata by age, sex, tobacco smoking, obstructive, and nonobstructive impairment on spirometry. A limitation of the current study is the observational nature of these findings and that causality cannot be inferred. CONCLUSIONS: We observed graded associations between lower FEV1 with higher odds of disabling respiratory symptoms, perceived poor general health, and lower cognitive and physical performance. These findings support the broader implications of measured lung function on general health and aging trajectory.

Nurses' knowledge, attitudes, and willingness to practice hospice care: An analysis of influencing factors.

BACKGROUND: Hospice care is a multidisciplinary approach that focused on patients' quality of life, and nurses allocate more of their time with patients and patients' families than those nurses working in other disciplines. Nurses' knowledge of and attitudes toward hospice care can affect the quality of hospice care. At present, China's hospice care institutions are suffering from an obvious shortage of nursing staff. Since clinical nurses are the main force behind the future provision of hospice care, their knowledge of, attitudes and willingness to practice can greatly promoted the growth of hospice care, however, available data on clinical nurses' willingness to practice hospice care are limited. METHODS: A cross-sectional descriptive study design was employed to collect data from 1833 nurses working in tertiary or secondary general hospitals in Guangxi, China. We examined nurses' demographic characteristics and scores on the Chinese version of the hospice care knowledge scale, the Chinese version of the Bradley Attitude Assessment Questionnaire, and a brief quiz concerning their willingness to practice hospice care in the future. Descriptive, single factor, multiple regression analyses and logistic regression analyses were used for data analysis. RESULTS: Nurses displayed moderate mean scores for both knowledge of and attitudes, and only 505 (27.5%) nurses expressed their willingness to practice hospice care, 1329 (72.5%) of nurses sampled expressed their unwillingness or uncertainty. Multivariate regression analyses showed that education, professional qualification, monthly income, whether they had been trained in hospice care, and willingness to practice hospice care were the main influencing factors of knowledge; education, whether they lived with someone aged >60 years, and whether they had been trained in hospice care were main factors influencing attitudes. Additionally, logistic regression analyses showed that hospice care knowledge, whether they had been trained in hospice care, and whether they had clinical experience affected the nurses' willingness to practice hospice care. CONCLUSION: This study highlighted a knowledge gap and moderate attitudes toward hospice care among nurses, and most nurses did not prefer to practice hospice care. Having been trained in hospice care was the main common factor of nurses' knowledge of, attitudes toward, and willingness to practice hospice care in the future, indicating the necessity to provide nurses with more targeted hospice care training.

Mapping research trends of insulin resistance in polycystic ovary syndrome from 2017 to 2021: A bibliometric analysis.

Introduction: To map publication trends and explore research hotspots of insulin resistance (IR) in polycystic ovary syndrome (PCOS) study. Methods: With the theme of "Polycystic ovary syndrome" AND "Insulin Resistance", the key data set of Science Core Literature Collection (WoSCC) web from 2017 to 2021 was extracted and bibliometric analysis was performed. Through VOSviewer v1.6.10 software, the research trend in this field is analyzed visually. Results: 2080 literatures about IR in PCOS from 2017 to 2021 were downloaded. The following basic information was collected for each article: country, author, institution, journal, references. The key words are divided into six categories: (1) The interaction between insulin resistance and chronic inflammation; (2) The relationship between insulin resistance and metabolic syndrome and nonalcoholic fatty liver disease; (3) The interaction between insulin resistance and hyperandrogenemia; (4) The relationship between insulin resistance and dyslipidemia; (5) Metformin may regulate insulin resistance in the treatment of PCOS; (6) The study of serum biomarkers in PCOS patients with insulin resistance. Discussion: The six key words extracted can provide an in-depth perspective for the study of IR in PCOS, and provide valuable information to help researchers identify potential research directions, collaborators and cooperative institutions.

Efficacy of Traditional Chinese Medicine on Animal Model of IgA Nephropathy: A Systematic Review and Meta-Analysis.

Objective: Traditional Chinese medicine (TCM) has a long history in the treatment of Immunoglobulin A nephropathy (IgAN). A large number of animal experiments focused on the TCM treatment of IgAN are conducted every year. The evidence for these preclinical studies is not clear. This study summarized and evaluated the results of animal experiments on TCM treatment for IgAN. Methods: We systematically searched animal studies from 6 databases from inception to August 30, 2022. We included Chinese studies from the key magazine of China technology. The quality of the included studies was evaluated with the SYRCLE animal experimental bias risk assessment tool and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results: Out of 832 records identified in the initial search, 30 studies were selected. The results indicated that, compared with the control group, the TCM treatment group improved 24 h urine protein (24 h-UP) level (standardized mean difference (SMD) 3.57, 95% confidence interval (CI) 4.48 to 2.66, P < 0.001), urine red blood cell (U-RBC) (SMD 13.66, 95% CI 17.99 to 9.32, P < 0.001), serum creatinine (Scr) (mean difference (MD) 10.89, 95% CI 17.00 to 4.77, P < 0.001), blood urea nitrogen (BUN) (MD 2.44, 95% CI 3.42 to 1.47, P < 0.001), tumor necrosis factor-α (TNF-α) (MD 171.28 to 95% CI 323.68 to 18.88, P=0.03), transforming growth factor-ß1 (TGF-ß) (SMD 4.02, 95% CI 7.26 to 0.77, P=0.02), matrix metalloproteinase-9/tissue inhibitors of metalloproteinase-1(MMP-9/TIMP-1) (MD 0.03, 95% CI 0.00 to 0.06, P=0.02), nephrin mRNA (SMD 3.39, 95% CI 2.59 to 4.18, P < 0.001). However, there is no difference in albumin level (MD 1.10, 95% CI 0.06 to 2.26, P=0.06) and interleukin-6 (IL-6) (MD 170.77, 95% CI 365.3 to 23.75, P=0.09). Conclusions: TCM can improve 24 h-UP, U-RBC, Scr, BUN, MMP-9/TIMP-1, TNF-α, TGF-ß, and nephrin mRNA of IgAN animal models. Moreover, there is a need for rigorous reporting of preclinical research methodology, which is essential to support the quality of preclinical research. Registration. This review was registered with a systematic review record CRD42020171404 in the PROSPERO database.

Associations of Adverse Childhood Experiences with Frailty in Older Adults: A Cross-Sectional Analysis of Data from the Canadian Longitudinal Study on Aging.

INTRODUCTION: Frailty in older adults, characterized by a decline in multiple physiological systems and increasing vulnerability to loss of independence, disability, and death, is a public health priority in developed countries. Etiology of frailty extends across the lifespan and may begin in early life, but empirical evidence for this association is scarce. In this study, we examined whether adverse childhood experiences (ACEs) are associated with frailty in later life. METHODS: We conducted a cross-sectional analysis of data for a population-based sample of 27,748 adults aged 45-85 years from the Canadian Longitudinal Study on Aging. The frailty index (FI) was computed with 76 health-related characteristics of physical and cognitive performance, self-rated health, chronic conditions, visual and hearing ability, activities of daily living, and well-being. Self-reported exposure to ACEs included physical, emotional, and sexual abuse, neglect, and witnessing intimate partner violence prior age of 16 and parental death, divorce, and living with a family member with mental illness prior age of 18. Generalized linear regression models with gamma error distribution and identity link function, adjusted for age and sex, were used to examine associations of each ACE type and the number of ACE types (0, 1, 2, or 3+) reported by an individual with FI. All models were adjusted for income, education, smoking, and alcohol consumption in sensitivity analysis. RESULTS: Individuals exposed to ACEs had elevated levels of FI (mean = 0.13, SD = 0.09) than those unexposed, with the largest difference observed for neglect (B [95% CI]: 0.05 [0.04, 0.06]) and the smallest for parental death and divorce (0.015 [0.01,0.02]). The ACE count was associated with frailty in a graded manner, with the FI difference reaching 0.04 [0.037, 0.044] for participants exposed to 3+ ACE types. The association between ACEs and frailty tended to be stronger for women than men and for men aged 45-64 years than older men. CONCLUSIONS: Our study supports previous studies showing that exposure to ACEs is associated with frailty in adults. Our findings suggest that screening for ACEs involving childhood maltreatment may be useful for identifying individuals at risk of frailty and prevention of ACEs may have long-term benefits for healthy aging.

[Progress of developmental mechanism of subtype H vessels in osteonecrosis of the femoral head].

OBJECTIVE: To review the research progress of subtype H vessels in the occurrence and development of osteonecrosis of the femoral head (ONFH). METHODS: The relevant domestic and foreign literature was extensively reviewed. The histological features, biological mechanism of subtype H vessels involved in promoting of osteogenesis, and the role and application of the subtype H vessels in ONFH were summarized. RESULTS: The subtype H vessel is a newly discovered bone vessel, mainly distributed in metaphysis and subperiosteum, highly expressing endomucin and CD31. The subtype H vessel has a dense arrangement of Runx2 + early osteoprogenitors, collagen type Ⅰα + osteoblast cells, and Osterix + osteoprogenitors that have the ability to induce osteogenesis and angiogenesis. Factors such as platelet-derived growth factor BB, slit guidance ligand 3, hypoxia inducible factor 1α, Notch signaling pathway, and vascular endothelial growth factor are involved in the mechanism of subtype H vessels in promoting osteogenesis. CONCLUSION: Subtype H vessels play an important role in the regulation of angiogenesis and osteogenesis during bone tissue repair and reconstruction. The discovery of subtype H vessels provides new insights into the molecular and cellular mechanisms of osteogenesis and angiogenesis coupling. In the future, new techniques targeting the regulation of subtype H blood vessels may become a promising method for the treatment of ONFH.

A Validated Risk Prediction Model for Bone Fragility in Children With Acute Lymphoblastic Leukemia.

Although bone fragility may already be present at diagnosis of pediatric acute lymphoblastic leukemia (ALL), routine performance of dual-energy X-ray absorptiometry (DXA) in every child is not universally feasible. The aim of this study was to develop and validate a risk prediction model for low lumbar spine bone mineral density (LS BMD Z-score ≤ -2.0) at diagnosis, as an important indicator for fracture risk and further treatment-related BMD aggravation. Children with ALL (4-18 years), treated according to the Dutch Childhood Oncology Group protocol (DCOG-ALL9; model development; n = 249) and children from the Canadian Steroid-Associated Osteoporosis in the Pediatric Population cohort (STOPP; validation; n = 99) were included in this study. Multivariable logistic regression analyses were used to develop the prediction model and to confirm the association of low LS BMD at diagnosis with symptomatic fractures during and shortly after cessation of ALL treatment. The area under the receiver operating characteristic curve (AUC) was used to assess model performance. The prediction model for low LS BMD at diagnosis using weight (ß = -0.70) and age (ß = -0.10) at diagnosis revealed an AUC of 0.71 (95% CI, 0.63-0.78) in DCOG-ALL9 and 0.74 (95% CI, 0.63-0.84) in STOPP, and resulted in correct identification of 71% of the patients with low LS BMD. We confirmed that low LS BMD at diagnosis is associated with LS BMD at treatment cessation (OR 5.9; 95% CI, 3.2-10.9) and with symptomatic fractures (OR 1.7; 95% CI, 1.3-2.4) that occurred between diagnosis and 12 months following treatment cessation. In meta-analysis, LS BMD at diagnosis (OR 1.6; 95% CI, 1.1-2.4) and the 6-month cumulative glucocorticoid dose (OR 1.9; 95% CI, 1.1-3.2) were associated with fractures that occurred in the first year of treatment. In summary, a prediction model for identifying pediatric ALL patients with low LS BMD at diagnosis, as an important indicator for bone fragility, was successfully developed and validated. This can facilitate identification of future bone fragility in individual pediatric ALL patients. © 2021 American Society for Bone and Mineral Research (ASBMR).

Respiratory Symptoms Are Associated With Frailty in Older Adults With Normal Spirometry, Independent of Smoking, in the Canadian Longitudinal Study of Aging.

BACKGROUND: Recent studies have demonstrated that even in the absence of lung impairment as determined by spirometry, smoking and respiratory symptoms are associated with poor overall health and well-being. However, this relationship is not well defined; and it remains unclear the degree to which symptoms are related to poor health, independent of smoking. This is of particular importance to older adults, as they are more likely to exhibit respiratory symptoms and are, therefore, at risk of not receiving appropriate treatment if they have never smoked and have normal spirometry. METHODS: We performed a cross-sectional analysis of data from the Canadian Longitudinal Study on Aging to delineate the associations of respiratory symptoms and smoking on the health of participants age 45-86 who exhibited normal spirometry. Participant health was estimated using a frailty index, a multidimensional measure of vulnerability to adverse outcomes that has been validated in numerous health settings. RESULTS: Of the 21,293 participants included in our analysis, 87% exhibited a normal FEV1, FVC, and FEV1/FVC; of those, 45% reported at least one respiratory symptom, and 50% were former or current smokers. Both respiratory symptoms and smoking were independently associated with frailty (median interquartile range [IQR] = 0.11 [0.07-0.15]), the most substantial associations observed for those having at least one respiratory symptom (adjusted ß 0.023, 95% CI 0.022-0.025) and current smokers with > 10 pack-year exposure (adjusted ß 0.014, 95% CI [0.010-0.019). Not only was the association between symptoms and frailty evident in never smokers, a significant proportion of the total effect of smoking on frailty was observed to be mediated by symptoms. CONCLUSIONS: Our data show that respiratory symptoms, regardless of smoking history, were a significant correlate of frailty in older adults with normal spirometry. Hence, they should not be simply regarded as a benign by-product of aging.

Derivation and validation of predictors of oral anticoagulant-related adverse events in seniors transitioning from hospital to home.

INTRODUCTION: Oral anticoagulant (OAC)-related adverse events are high post-hospitalization. We planned to develop and validate a prediction model for OAC-related harm within 30 days of hospitalization. METHODS: We undertook a population-based study of adults aged ≥66 years who were discharged from hospital on an OAC from September 2010 to March 2015 in Ontario, Canada. The primary outcome was a composite of time to first hospitalization or emergency department visit for a hemorrhagic or thromboembolic event, or mortality within 30 days of hospital discharge. Cox proportional hazards regression was used to build the model. RESULTS: We included 120,721 patients of which 5423 experienced the outcome. Most patients were aged ≥75 years (59.5%) and were female (55.6%). Sixty percent of the cohort had a follow-up visit with a healthcare provider within 7 days of discharge. Patients discharged on a direct acting OAC versus warfarin (apixaban: Hazard Ratio [HR] 0.82, 95% confidence interval [CI] 0.71-0.94; dabigatran: HR 0.73, 95% CI 0.63-0.84; rivaroxaban: HR 0.79, 95% CI 0.71-0.88), were prevalent users of the dispensed OAC versus incident users (HR 0.82, 95% CI 0.69-0.96), had a joint replacement in the past 35 days (HR 0.40, 95% CI 0.33-0.50) or major surgery during index hospital stay (HR 0.69, 95% CI 0.60-0.80) had a lower risk for the outcome. The Cox model was stable with acceptable discrimination but poor goodness-of-fit. CONCLUSIONS: A model for OAC-related harm in the early post-discharge period was developed. External validation studies are required to understand the model's poor calibration.

Autologous Osteochondral Transplantation for Young Patients with Postcollapse Osteonecrosis of the Knee: A Retrospective Cohort Study with an Average 7-Year Follow-Up.

BACKGROUND: Only a few studies exist that have assessed the efficacy of autologous osteochondral transplantation (AOT) treatment of osteonecrosis (ON) of the knee. The purpose of this study was to clarify the clinical and radiographic results of AOT performed on young patients with postcollapse ON of the knee. METHODS: This retrospective study included 14 young patients (6 men, 8 women, mean age 34.71 ± 5.41 years) with stage III knee ON undergoing AOT surgery. Mean follow-up time was 87 ± 10.23 months. The postoperative clinical and radiological evaluations were based on Hospital for Special Surgery (HSS) scores and plain x-rays. Paired t tests were used for the statistical analysis by SPSS software. RESULTS: Preoperative HSS (mean 66.86 ± 7.49 points) was significantly improved at mean 7 years to a postoperative HSS (mean 87.36 ± 8.63 points) (P < 0.001). The postoperative rangeof motion (ROM; 125.71° ± 4.74°) was not significantly different from the preoperative ROM (126.86° ± 7.13°) (P = 0.626). There was no progression of collapse observed in any knees at the last follow-up. No knees required any reoperations during the follow-up period. CONCLUSION: Fourteen young patients with local ON of the knee were treated by AOT. No progression of bone collapse was seen and clinical improvement sustained at mean 7 years postsurgery. AOT seems to be a safe technique that can give long-term improvement and durability in young ON patients. However, large-sample and high-quality clinical trials are still needed in the future.

The combined effect of behavioural risk factors on disability in aging adults from the Canadian Longitudinal Study on Aging (CLSA).

The objective of this study was to explore how behavioural risk factors (smoking, physical activity, and nutrition) cluster together and assess how clusters of behavioural risk factors are associated with functional disability by age and sex at the individual and population level. We used currently available baseline cross-sectional data from the Canadian Longitudinal Study on Aging (CLSA). The CLSA is a national, population-based longitudinal study established to understand and examine health of an aging population. This study included 51,338 Canadian men and women aged 45 to 85 years residing in the community in 10 Canadian provinces. Behavioural risk factors included smoking, physical activity, and nutrition. The main outcome used in the study was functional disability, which was assessed using a questionnaire adapted from the Older Americans Resources and Services Multidimensional Assessment Questionnaire. In this analyses of unique combinations of the risk factors of smoking, physical activity, and nutritional risk, the magnitude of the association of the behavioural risk factors with functional disability was dependent on which risk factors were included and differed by age and sex strata. Of the risk factors, physical activity accounted for between 70% to 90% of the total population level risk in individuals with all three risk factors, suggesting it is a key driver of the population burden of disability. Together, these results show that considering unique clusters of risk factors, as well as age and sex, is essential for tailoring public health strategies to reduce the burden of disability among aging populations.

The Accuracy of Incident Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches.

Vertebral fractures are clinically important sequelae of a wide array of pediatric diseases. In this study, we examined the accuracy of case-finding strategies for detecting incident vertebral fractures (IVF) over 2 years in glucocorticoid-treated children (n = 343) with leukemia, rheumatic disorders, or nephrotic syndrome. Two clinical situations were addressed: the prevalent vertebral fracture (PVF) scenario (when baseline PVF status was known), which assessed the utility of PVF and low lumbar spine bone mineral density (LS BMD; Z-score <-1.4), and the non-PVF scenario (when PVF status was unknown), which evaluated low LS BMD and back pain. LS BMD was measured by dual-energy X-ray absorptiometry, vertebral fractures were quantified on spine radiographs using the modified Genant semiquantitative method, and back pain was assessed by patient report. Forty-four patients (12.8%) had IVF. In the PVF scenario, both low LS BMD and PVF were significant predictors of IVF. Using PVF to determine which patients should have radiographs, 11% would undergo radiography (95% confidence interval [CI] 8-15) with 46% of IVF (95% CI 30-61) detected. Sensitivity would be higher with a strategy of PVF or low LS BMD at baseline (73%; 95% CI 57-85) but would require radiographs in 37% of children (95% CI 32-42). In the non-PVF scenario, the strategy of low LS BMD and back pain produced the highest specificity of any non-PVF model at 87% (95% CI 83-91), the greatest overall accuracy at 82% (95% CI 78-86), and the lowest radiography rate at 17% (95% CI 14-22). Low LS BMD or back pain in the non-PVF scenario produced the highest sensitivity at 82% (95% CI 67-92), but required radiographs in 65% (95% CI 60-70). These results provide guidance for targeting spine radiography in children at risk for IVF. © 2021 American Society for Bone and Mineral Research (ASBMR).

Intra-articular magnesium to alleviate postoperative pain after arthroscopic knee surgery: a meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to evaluate the safety and efficacy of intra-articular (IA) magnesium (Mg) for postoperative pain relief after arthroscopic knee surgery. METHODS: We searched PubMed, Embase, Medline, Cochrane library, and Web of Science to identify randomized controlled trials that compared postoperative pain outcomes with or without IA Mg after knee arthroscopy. The primary outcomes were pain intensity at rest and with movement at different postoperative time points and cumulative opioid consumption within 24 h after surgery. Secondary outcomes included the time to first analgesic request and side effects. RESULTS: In total, 11 studies involving 677 participants met the eligibility criteria. Pain scores at rest and with movement 2, 4, 12, and 24 h after surgery were significantly lower, doses of supplementary opioid consumption were smaller, and the time to first analgesic requirement was longer in the IA Mg group compared with the control group. No significant difference was detected regarding adverse reactions between the groups. CONCLUSIONS: Intra-articular magnesium is an effective and safe coadjuvant treatment for relieving postoperative pain intensity after arthroscopic knee surgery. Protocol registration at PROSPERO: CRD42020156403.

Lower early revision rates after uncemented Oxford Unicompartmental Knee Arthroplasty (UKA) than cemented Oxford UKA: A meta-analysis.

BACKGROUND: UKA has been proved to offer good results in treating patients with unicompartmental knee osteoarthritis (OA). However, there is still a controversy about the better fixation mode in UKA procedure between cemented and uncemented prosthesis. Therefore, this meta-analysis was conducted to compare clinical and radiological outcomes of cemented versus uncemented Oxford UKA. HYPOTHESIS: The study surmised that uncemented Oxford UKA was associated with shorter operation time, higher function scores, lower revision rate and less radiolucency than cemented Oxford UKA. METHODS: A meta-analysis to compare postoperative outcomes between cemented and uncemented Oxford UKA wsa conducted. The primary outcomes included Oxford knee score (OKS), revision rate, and incidence of radiolucency. The secondary outcomes included operation time, knee society score (KSS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), range of motion (ROM). PubMed, Embase, Web of Science, the Cochrane Library and China national knowledge infrastructure were searched until April, 2020 to identify studies for including. Relevant data were analyzed using RevMan v5.3. RESULTS: We identified nine studies involving 901 patients meeting our inclusion criteria. No significant difference of OKS was found in both groups. Compared with cemented group, uncemented Oxford UKA group was associated with lower revision rate (95% CI: 0.90 to 3.73; OR=1.83) and less radiolucent lines (95% CI: 0.79 to 9.52; OR=2.75) after following up for at least 2years. The operation time was significantly shorter by 10.12minutes (95% CI: p<0.00001) in the uncemented group when compared against the cemented group. The KSS, WOMAC, ROM were not significantly different between two groups. CONCLUSIONS: Uncemented Oxford UKA had lower revision rate, shorter operation time and less radiolucent lines than cemented Oxford UKA did. There is still need for more long follow-up clinical trials with high evidence level to determine which method of fixation is of preferable for Oxford UKA in the future. LEVEL OF EVIDENCE: I.