Establishing a Chinese older hip fracture registry for older patients: a Delphi study to define the focus and key variables for this registry.

A national hip fracture registry does not yet exist in China. This is the first to recommend a core variable set for the establishment of a Chinese national hip fracture registry. Thousands of Chinese hospitals will build on this and improve the quality of management for older hip fracture patients. The rapidly ageing population of China already experiences over half a million hip fractures every year. Many countries have developed national hip fracture registries to improve the quality of hip fracture management, but such a registry does not exist in China. The study is aimed at determining the core variables of a national hip fracture registry for older hip fracture patients in China. A rapid literature review was conducted to develop a preliminary pool of variables from existing global hip fracture registries. Two rounds of an e-Delphi survey were conducted with experts. The e-Delphi survey used a Likert 5-point scale and boundary value analysis to filter the preliminary pool of variables. The list of core variables was finalised following an online consensus meeting with the experts. Thirty-one experts participated. Most of the experts have senior titles and have worked in a corresponding area for more than 15 years. The response rate of the e-Delphi was 100% for both rounds. The preliminary pool of 89 variables was established after reviewing 13 national hip fracture registries. With two rounds of the e-Delphi and the expert consensus meeting, 86 core variables were recommended for inclusion in the registry. This study is the first to recommend a core variable set for the establishment of a Chinese national hip fracture registry. The further development of a registry to routinely collect data from thousands of hospitals will build on this work and improve the quality of management for older hip fracture patients in China.

Montreal cognitive assessment (MoCA) is highly correlated with 1-year mortality in hip fracture patients.

Prevalence of cognitive impairment in hip fractures was 86.5%. MoCA is an independent risk factor of mortality. MoCA score of < 15 is correlated with 11.71 times increased risk of mortality. Early attention and caution should be given to these patients for appropriate intervention to decrease mortality rates. INTRODUCTION: Hip fractures rank amongst the top 10 causes of disability and current mortality of hip fractures is high. Objectives were to determine 1) prevalence of cognitive impairment, 2) whether Montreal Cognitive Assessment (MoCA) score was an independent risk factor associated with mortality, 3) MoCA cut-off that result in high risk of mortality. METHODS: This was a cohort study between July 2019 to June 2020. Inclusion criteria were 1) hip fracture, 2) > = 65 years old, and 3) low-energy trauma. Patients undergo assessment for cognitive impairment with MoCA. Prevalence was assessed, MoCA cut-off point, and accuracy of statistical model was evaluated. Logistic regression modelling was used to assess association between mortality and MoCA. RESULTS: There were 260 patients recruited. Two hundred twenty-five patients had MoCA score < 22 signifying cognitive impairment, and 202 patients had MoCA score of < 19. 46 hip fracture patients died at 1-year follow-up. 45 of these patients had MoCA score < 19, and 1 patient had a MoCA > 22. Results showed statistical significance and good model effect (at least 0.8) with MoCA cut-off points between < 15 and < 19 (p < 0.05). After controlling confounding factors, statistical significance still existed in MoCA cut-off point at < 15 (odds ratio (95% CI) = 11.71 (1.14, 120.71); p = 0.04). CONCLUSION: Prevalence of cognitive impairment in hip fractures was 86.5%. MoCA is an independent risk factor of mortality in hip fracture patients. MoCA score of < 15 is correlated with 11.71 times increased risk of mortality at 1-year after a hip fracture. AUC with MoCA score < 15 was 0.948. Early attention and caution should be given to these patients for appropriate intervention to decrease mortality rates.

The effectiveness of exercises on fall and fracture prevention amongst community elderlies: A systematic review and meta-analysis.

OBJECTIVE: To analyze the effectiveness of exercise interventions on falls and fall-related fracture prevention among community-dwelling elderlies. METHODS: Literature search was conducted in Pubmed and Embase. Keywords used for literature search were "fracture" AND "fall" AND "exercise". Randomized controlled trials involving community-dwelling elderlies older than 60 years old with physical exercises as intervention were included. A systematic review and meta-analysis was performed. The primary outcomes were falls and fractures. RESULTS: Twelve studies were included and 4784 participants were involved with a mean age of 75.4. The most common exercise interventions were strength and balance exercises. The results of meta-analysis of 11 studies showed that exercise intervention had beneficial effect on fall prevention (RR = 0.71, 95% CI, 0.62-0.82; I2 = 24%, p < 0.0001). The effect was better when exercise intervention applied to women participants (RR = 0.64, 95% CI, 0.49-0.83; I2 = 28%, p = 0.00009) compared to men and women participants (RR = 0.75, 95% CI, 0.64-0.89; I2 = 24%, p = 0.001). The results of meta-analysis of seven studies showed that physical exercise had significant effect on fracture prevention (RR = 0.54, 95% CI, 0.35-0.83; I2 = 25%, p = 0.005). However, the effect was significant when exercise intervention applied to women participants only (RR = 0.37, 95% CI, 0.20-0.67; I2 = 0%, p = 0.001) but not significant when exercise intervention applied to both genders (RR = 0.80, 95% CI, 0.58-1.09; I2 = 0%, p = 0.15). CONCLUSION: Exercise interventions, especially the combination of strength and balance training, were effective in preventing falls. Resistance exercises and jumping exercises were effective for fracture prevention among community-dwelling older population. The effectiveness of exercise interventions on fracture prevention have more significant effect on women. Further studies are needed to test the effectiveness of exercise interventions in men. TRANSLATIONAL POTENTIAL: The use of effective exercises or biophysical interventions including vibration therapy can be incorporated into Fracture Liaison Services to prevent future fall and fracture.

Vibration treatment modulates macrophage polarisation and enhances early inflammatory response in oestrogen-deficient osteoporotic-fracture healing.

Fracture healing is a well-orchestrated and coordinated process and begins with the inflammatory stage involving the infiltration of immune cells and the release of cytokines, including tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-10 (IL-10). Low-magnitude high-frequency vibration (LMHFV) stimulation is effective in promoting fracture healing. The study hypothesis was that the innate immune response was impaired in osteoporotic fracture and LMHFV could positively modulate it. 9-month-old ovariectomy (OVX)-induced osteoporotic rats were randomised into sham (SHAM), OVX control (OVX), OVX-vibration (OVX-VT) or OVX vibration plus administration of COX-2 specific non-steroid anti-inflammatory drugs (OVX-VT-NSAID). LMHFV (35 Hz, 0.3 g) was given 20 min/d and 5 d/week to the treatment groups. Healing and innate immune response were evaluated by weekly radiographs, endpoint micro-computed tomography (µCT), enzyme-linked immunosorbent assay (ELISA) and histomorphometry at weeks 1, 2, 4 and 8 post-treatment. Results showed that OVX slightly elevated systemic inflammation but impaired the innate immune response locally at the fracture site, with significantly lower expressions of TNF-α and IL-6 but higher IL-10 expression during the early stage of healing. LMHFV was effective in accelerating the delayed fracture healing in OVX bones by partly restoring the impaired innate immune response at the fracture site, accompanied by promoted progression of macrophage polarisation from M1 (pro-inflammatory) to M2 (anti-inflammatory) phenotype. In conclusion, vibration treatment could positively modulate the impaired innate immune response and promote macrophage polarisation in osteoporotic-fracture healing.

A metaphyseal fracture rat model for mechanistic studies of osteoporotic bone healing.

Most osteoporotic fractures occur at metaphyseal regions of long bones. The present study proposed a clinically relevant animal model that satisfied: i) induction of osteoporosis, ii) unilateral complete osteotomy at metaphysis, iii) internal fixation. 6 months old female Sprague-Dawley rats (n = 64) were randomly divided into the ovariectomised-metaphyseal osteotomy (OVX, n = 32) and metaphyseal osteotomy (SHAM, n = 32) groups. The metaphyseal-osteotomy model was created with a plate-fixation of the osteotomy and assessed by X-ray, micro-computed tomography, histomorphometry and mechanical testing at weeks 1, 3 and 6. X-ray results showed complete healing of metaphyseal osteotomy at week 6. Histology showed 3 stages of metaphyseal healing. Stage 1 was characterised by fibrous tissue, consisting of disorganised orientation of collagen fibres, and infiltration of immune cells. At stage 2, a transitional zone consisting of maturing fibrous tissue and differentiating mesenchymal cells with early trabecular bone formation and disorganised woven bone were observed. During stage 3, cortical bone ends unified and woven bone underwent transformation to lamellar bone. OVX group healing was significantly delayed when compared to SHAM samples. The study demonstrated that healing of osteoporotic osteotomy at the metaphyseal region was delayed in terms of radiography, histomorphometry and mechanical strength. These quantitative evaluations, along with histological features, may provide key references for future studies. The animal model may provide additional clinical relevance as most osteoporotic fracture in humans occurs at metaphyseal regions.

The relationship between sarcopenia and fragility fracture-a systematic review.

Sarcopenia is a common geriatric syndrome characterized by progressive decrease of muscle mass and function leading to an increased risk of physical disability, poor quality of life, and mortality. Increasing evidence shows that sarcopenia is related with fragility fractures. This systematic review aimed to summarize the following: (1) the prevalence of sarcopenia in patients with fragility fracture and (2) the associated risk factors for fragility fracture in patients with sarcopenia. Literature search was conducted in PubMed and Cochrane databases. Studies with the prevalence of sarcopenia in elderly patients with fragility fracture and associated risk factors in patients with sarcopenia were included. A total of 15 papers were included, with 10 reporting sarcopenia prevalence, and 5 on fracture risk in patients with sarcopenia. The prevalence of sarcopenia after fracture ranged from 12.4 to 95% in males and 18.3 to 64% in females. The prevalence of sarcopenia in elderly patients with fragility fracture was high, especially in men. Two studies showed that sarcopenia was a risk factor for fragility fracture when associated with low bone mineral density (BMD) but only in men. Caution should be taken for male patients with sarcopenia and low BMD, which is related to significantly increased risk of fractures. There is a pressing need for further research on sarcopenia and its risk on fragility fracture to better understand the relationship, pathophysiology, and mechanisms, which may shed light on potential interventions to improve clinical outcomes.

Jaundice in infants and children: causes, diagnosis, and management.

Jaundice is caused by an accumulation of bilirubin in the blood. The presentation in infants and children can be indicative of a wide range of conditions, with some self-limiting and others potentially life-threatening. This article aims to provide a concise review of the common medical and surgical causes in children and discuss their diagnosis and management.

A systematic review of current osteoporotic metaphyseal fracture animal models.

OBJECTIVES: The treatment of osteoporotic fractures is a major challenge, and the enhancement of healing is critical as a major goal in modern fracture management. Most osteoporotic fractures occur at the metaphyseal bone region but few models exist and the healing is still poorly understood. A systematic review was conducted to identify and analyse the appropriateness of current osteoporotic metaphyseal fracture animal models. MATERIALS AND METHODS: A literature search was performed on the Pubmed, Embase, and Web of Science databases, and relevant articles were selected. A total of 19 studies were included. Information on the animal, induction of osteoporosis, fracture technique, site and fixation, healing results, and utility of the model were extracted. RESULTS: Fracture techniques included drill hole defects (3 of 19), bone defects (3 of 19), partial osteotomy (1 of 19), and complete osteotomies (12 of 19). Drill hole models and incomplete osteotomy models are easy to perform and allow the study of therapeutic agents but do not represent the usual clinical setting. Additionally, biomaterials can be filled into drill hole defects for analysis. Complete osteotomy models are most commonly used and are best suited for the investigation of therapeutic drugs or noninvasive interventions. The metaphyseal defect models allow the study of biomaterials, which are associated with complex and comminuted osteoporotic fractures. CONCLUSION: For a clinically relevant model, we propose that an animal model should satisfy the following criteria to study osteoporotic fracture healing: 1) induction of osteoporosis, 2) complete osteotomy or defect at the metaphysis unilaterally, and 3) internal fixation.Cite this article: R. M. Y. Wong, M. H. V. Choy, M. C. M. Li, K-S. Leung, S. K-H. Chow, W-H. Cheung, J. C. Y. Cheng. A systematic review of current osteoporotic metaphyseal fracture animal models. Bone Joint Res 2018;7:6-11. DOI: 10.1302/2046-3758.71.BJR-2016-0334.R2.

Increased arterial stiffness in patients with psoriasis is associated with active systemic inflammation.

BACKGROUND: Psoriasis is associated with premature atherosclerosis although the underlying mechanism remains unclear. OBJECTIVES: We sought to investigate the relationship between disease activity and systemic inflammation in patients with psoriasis, and macrovascular and microvascular function. METHODS: Fifty-two patients with psoriasis (mean ± SD age 44 ± 8 years; 38 men) were compared with 50 age- and sex-matched controls. Baseline demographics and high-sensitivity C-reactive protein (hs-CRP) level were recorded for each subject. Psoriatic disease activity was assessed using the Psoriasis Area and Severity Index (PASI). Arterial stiffness and endothelial function were assessed using brachial to ankle pulse wave velocity (baPWV) and digital hyperaemic response measured using the peripheral arterial tonometry (PAT) index. RESULTS: Patients with psoriasis had significantly higher hs-CRP (mean ± SD 5·3 ± 5·1 vs. 1·9 ± 1·6 mg L(-1), P < 0·01) and baPWV (mean ± SD 14·5 ± 2·5 vs. 13·2 ± 1·6 m s(-1) , P < 0·01) but not PAT index (mean ± SD 2·06 ± 0·59 vs. 2·10 ± 0·44, P = 0·70) than controls. There was significant correlation of hs-CRP with baPWV (r = 0·51, P < 0·01) and with PASI (r = 0·48, P < 0·01). Multiple linear regression analysis demonstrated that baPWV is independently correlated with age, fasting glucose and hs-CRP (P < 0·05), but does not predict PAT index. Each mg L(-1) increase in hs-CRP accounted for an increase in baPWV of +0·12 m s(-1) (95% confidence interval 0·01-0·22, P = 0·03). CONCLUSIONS: Young patients with psoriasis have increased arterial stiffness but not microvascular dysfunction compared with healthy controls. More importantly, hs-CRP positively correlated with, and independently predicted, arterial stiffness. This suggests that systemic inflammation in patients with psoriasis is associated with premature atherosclerosis.

Clinical experience in managing pediatric patients with ultra-short bowel syndrome using omega-3 fatty acid.

Total parenteral nutrition (TPN) remains an important component of the management of short bowl syndrome in pediatric patients. However, prolonged TPN is known to be associated with cholestasis. Recently, the use of omega-3-fatty acid (Omegaven) has been proposed to improve TPN cholestasis. We present the early outcome after administration of Omegaven in four patients with ultra-short bowel syndrome. Based on our experience, it appears that omega-3 fatty acid can reverse and prevent the advent of TPN-related cholestasis, thereby significantly improving the process of intestinal adaptation. We suggest that clinicians consider this treatment option before proceeding to invasive surgery to reverse cholestasis. Prospective randomized trials are necessary to define a standard protocol and elucidate other potential benefits of this novel agent.

Long-term follow-up of patients with diffuse large B-cell non-Hodgkin's lymphoma receiving purged autografts after induction failure.

Patients with diffuse large B-cell lymphoma (DLBCL) who do not achieve a complete response to front-line combination chemotherapy are often offered high-dose therapy and autologous hematopoietic cell transplantation (AHCT). However, the efficacy of this therapy in this patient population has been addressed in only a few published reports. We retrospectively analyzed the outcomes of patients with a diagnosis of de novo DLBCL who underwent AHCT at our center between 1988 and 2002, and identified 43 consecutive patients who had not achieved a CR before AHCT, although most showed at least a partial response (PR) to either induction or subsequent salvage chemotherapy. A total of 15 patients received a conditioning regimen that included high-dose chemotherapy with fractionated TBI (FTBI), whereas 28 patients received high-dose chemotherapy only. All autografts were treated ex vivo with MoAbs and complement in an effort to remove any residual malignant B cells. A total of 33 (77%) patients achieved a CR after AHCT. With a median follow-up of 7.3 years, the 5-year OS was 69% and EFS was 59%. Four patients died from non-relapse mortality. By univariate analyses, the following characteristics did not significantly impact OS: disease stage at diagnosis, age-adjusted IPI (International Prognostic Index) score, age > or =40 years, earlier radiotherapy and the use of FTBI in the conditioning regimen. These results confirm the long-term efficacy of AHCT for patients with DLBCL after induction failure.

Neurological manifestations in Japanese Ama divers.

Repetitive breath-hold (BH) diving can lead to accumulation of nitrogen (N2) in blood and tissues, which may give rise to decompression illness (DCI). An unusual condition is "Taravana", the diving syndrome reported by Cross in the 1960s. That report generated wide discussion as to whether BH diving can cause DCI. Paulev was the first person to suggest the link between DCI and BH diving. He, a submarine medical officer developed symptoms of DCI after a series of BH dives, having proceeded the dives by spending time in a hyperbaric chamber at 20 meters for 8 minutes. Recently four professional Japanese BH divers (Ama) with histories of diving accidents were reported. Magnetic resonance imaging of these divers detected cerebral infarcts localized in the watershed areas of the brain. A survey conducted on their island revealed that many Ama divers had experienced stroke-like events. A clinical feature of DCI in BH diving is that the damage is limited to the brain. Although the mechanisms of brain damage in BH diving are unclear, N2 bubbles passing through the lungs or the heart so as to become arterialized are most likely to be the etiological factor.

The DeltauvrB mutations in the Ames strains of Salmonella span 15 to 119 genes.

The DeltauvrB mutations present in strains of Salmonella enterica Typhimurium used commonly in the Salmonella (Ames) mutagenicity assay were isolated independently for at least five different his mutants. These deletions all involved the galactose operon, biotin operon, nucleotide-excision-repair uvrB gene, and chlorate-resistance genes. Beyond this, the size of the deletions and the number and type of genes deleted have remained unknown for nearly 30 years. Here, we have used genomic hybridization to a Typhimurium microarray to characterize these five DeltauvrB deletions. The number of genes (and amount of DNA) deleted due to the DeltauvrB mutations are 15 (16kb) each in TA97 and TA104, 47 (50kb) in TA100, 87 (96kb) in TA1537, and 119 (125kb) in TA98, accounting for 0.3, 0.3, 1.0, 1.9, and 2.6% of the genome, respectively. In addition, TA97 and TA104 contain an identical three-gene deletion elsewhere in their genomes, and, most remarkably, TA104 contains a 282-gene amplification, representing 7% of the genome. Missing genes include mfdA and mdaA, encoding a multi-drug translocase and a major nitroreductase, respectively, both absent in TA98; dps, encoding a DNA-binding protein absent in TA1537 and TA98; and dinG, encoding a lexA-regulated repair enzyme, absent in three DeltauvrB lineages. Genes involved in molybdenum cofactor biosynthesis and a number of ORFs of unknown functions are missing in all DeltauvrB strains investigated. Studies in DeltauvrB strains of Escherichia coli have found that the enhanced mutagenesis of some base analogues was due to the deletion of genes involved in molybdenum cofactor biosynthesis rather than to deletion of uvrB. These discoveries do not diminish the value of the data generated in the Ames strains. However, absence of genes other than uvrB may account for the enhanced mutagenicity of some compounds in DeltauvrB Ames strains. In general, microarrays will be useful for characterizing the extent and nature of deletion and amplification mutations.

High-dose therapy and autologous hematopoietic cell transplantation in children with primary refractory and relapsed Hodgkin's disease: atopy predicts idiopathic diffuse lung injury syndromes.

The use of high-dose therapy (HDT) and autologous hematopoietic cell transplantation (AHCT) for children and adolescents with primary refractory and relapsed Hodgkin's disease is increasing. The purpose of this retrospective analysis was to: (1) evaluate the outcome of HDT and AHCT in pediatric patients with Hodgkin's disease, and (2) identify factors that predispose patients to the development of transplantation-related complications. We describe the experiences of 34 pediatric patients from a single institution with primary refractory or relapsed Hodgkin's disease. HDT regimens consisted of cyclophosphamide and etoposide combined with either carmustine, chloroethylcyclohexylnitrosurea, or fractionated total body irradiation. Kaplan-Meier survival predicts that 67% (95% confidence interval [CI] 47%-87%) of patients will be alive and disease-free at 5 years. Nine patients had disease recurrence, of whom 5 relapsed after 1 year (1.5-6.3 years). Five patients succumbed to treatment-related toxicities, of whom 4 died of pulmonary failure. Fifteen patients (44%) developed post-AHCT idiopathic diffuse lung injury syndrome: acute alveolitis (n = 2); diffuse alveolar hemorrhage (n = 2); acute respiratory distress syndrome (n = 2); delayed interstitial pneumonitis (n = 8); and bronchiolitis obliterans (n = 1). The following factors did not predict for the development of a diffuse lung injury syndrome in univariate analysis: prior treatment with bleomycin, pre-HDT pulmonary function tests, and prior thoracic irradiation. Of the patients in our cohort, 44% had a history of atopy (allergic rhinitis and/or asthma). Multivariate logistic analysis revealed that a preexisting history of atopy was highly predictive of idiopathic pulmonary complications (P = .0001, odds ratio = 21, CI 3.6-125). Our experience shows that HDT followed by AHCT results in durable remissions in two thirds of pediatric patients with refractory and relapsed Hodgkin's disease, and a history of atopy is associated with post-AHCT pulmonary complications.

Efficacy and toxicity of a CCNU-containing high-dose chemotherapy regimen followed by autologous hematopoietic cell transplantation in relapsed or refractory Hodgkin's disease.

High-dose CBV (cyclophosphamide, carmustine, and etoposide) in combination with autologous HCT achieves survival rates of approximately 50% at 5 years in recurrent or refractory Hodgkin's disease (HD). However, carmustine (BCNU) dose-dependent pulmonary toxicity occurs in 20% to 30% of patients. A decreased incidence of interstitial pneumonitis as well as a possible benefit in efficacy has been reported with lomustine (CCNU) compared to BCNU in the standard dose setting. In a dose-escalation study, we substituted CCNU for BCNU in the CBV regimen for 16 patients with HD (n = 12) or non-Hodgkin's lymphoma (n = 4). Based on the promising results, an additional 47 consecutive patients with HD were treated with the following regimen: CCNU (15 mg/kg) orally on day -6, etoposide (60 mg/kg) intravenously on day -4, and cyclophosphamide (100 mg/kg) intravenously on day -2. Peripheral blood progenitor cells and/or bone marrow were infused on day 0. With a median follow-up for the surviving patients of 3.2 years (range, 0.8-9.9 years), the 3-year overall survival rate was 57% (CI, +/-15%), event-free survival was 52% (CI, +/-14%), and freedom from progression was 68% (CI, +/-14%). There were 21 deaths, 10 due to HD. Six patients died due to respiratory failure. Interstitial pneumonitis occurred in 63% of patients and could not be correlated with prior chest radiotherapy. This regimen demonstrated survival rates similar to those of historical studies that used the CBV regimen. However, the incidence of interstitial pneumonitis was in excess of expected.

Missense mutations of the fibrillin-1 gene in two Chinese patients with severe Marfan syndrome.

OBJECTIVE: To describe two Chinese patients with severe forms of Marfan syndrome and to report findings of mutational analysis of the fibrillin-1 (FBN1) gene. METHODS: Two Chinese patients were studied, one suffering from Marfan syndrome of infantile onset and the other of neonatal onset. Their clinical features were described. Mutational analysis of the FBN1 gene was performed using polymerase chain reaction (PCR) technique and direct sequencing of exons 23-32, where the mutational hotspots for severe forms of Marfan syndrome are located. RESULTS: Two missense mutations were successfully identified, a G3037A transition and an A3083T transversion, the latter being an unreported mutation. CONCLUSION: Taking advantage of the clustering phenomenon of mutations in severe forms of marfan syndrome, one can identify FBN1 mutations in these patients by first screening the mutational hotspots, thus reducing the effort that would otherwise be much greater because of the size of the gene.