Age- and gender-related normative value of whole-body sagittal alignment based on 584 asymptomatic Chinese adult population from age 20 to 89.

To establish the age- and sex-related normative values of sagittal alignment in asymptomatic Chinese adults, and to investigate the changes and possible associated compensation mechanisms across age groups. 584 asymptomatic Chinese adults aged 20-89 years were recruited. Subjects were grouped according to age and gender. Whole-body standing radiographs were acquired for evaluating sagittal alignment from spine to lower limb. Sagittal parameters between gender in different age groups were compared via independent t test. Pearson correlation analysis was used to demonstrate relationships between parameters. Thoracic kyphosis (TK) increased steadily while lumbar lordosis decreased gradually in both genders. Pelvic tilt (PT) in male is greater than in female across all age groups with age related gradual increase. There were significant differences between male and female from 20s to 60s in terms of knee flexion angle (KA) and ankle dorsiflexion angle (AA), but the differences were not significant after 60s. T1 pelvic angle (TPA) was significantly correlated with spinal, pelvic and lower-limb alignment. The older group (≥50 years) had a stronger correlation of TPA with PT and KA, whereas the younger (<50 years) had stronger correlation with TK. This study comprehensively presented the normative sagittal alignment based on a large asymptomatic population, which could serve as an age- and gender-specific reference value for spine surgeons when planning for correction surgery. Age can influence the recruitment of compensation mechanism that involve more pelvic and lower limb mechanisms for elderly people.

Core outcome set for surgical trials in gastric cancer (GASTROS study): international patient and healthcare professional consensus.

BACKGROUND: Surgery is the primary treatment that can offer potential cure for gastric cancer, but is associated with significant risks. Identifying optimal surgical approaches should be based on comparing outcomes from well designed trials. Currently, trials report different outcomes, making synthesis of evidence difficult. To address this, the aim of this study was to develop a core outcome set (COS)-a standardized group of outcomes important to key international stakeholders-that should be reported by future trials in this field. METHODS: Stage 1 of the study involved identifying potentially important outcomes from previous trials and a series of patient interviews. Stage 2 involved patients and healthcare professionals prioritizing outcomes using a multilanguage international Delphi survey that informed an international consensus meeting at which the COS was finalized. RESULTS: Some 498 outcomes were identified from previously reported trials and patient interviews, and rationalized into 56 items presented in the Delphi survey. A total of 952 patients, surgeons, and nurses enrolled in round 1 of the survey, and 662 (70 per cent) completed round 2. Following the consensus meeting, eight outcomes were included in the COS: disease-free survival, disease-specific survival, surgery-related death, recurrence, completeness of tumour removal, overall quality of life, nutritional effects, and 'serious' adverse events. CONCLUSION: A COS for surgical trials in gastric cancer has been developed with international patients and healthcare professionals. This is a minimum set of outcomes that is recommended to be used in all future trials in this field to improve trial design and synthesis of evidence.

Nasal septal angiofibroma: less vascular behaviour than observed in radiological imaging, a rare case in a 51-year-old woman.

Angiofibroma of the head and neck is classically found in the nasopharynx of an adolescent male. We present a rare case where an angiofibroma was diagnosed in the anterior nasal septum of a 51-year-old woman, the eighth nasal septal angiofibroma reported in a female. This case highlights how an angiofibroma in an older woman has a less vascular behaviour than one in an adolescent male, even though radiological enhancement may suggest that the lesion is highly vascularised. Nasal septal angiofibromas can be managed by biopsy and removed by simple endoscopic resection with minimal haemorrhage. Although very rare, extranasopharyngeal angiofibroma/nasal septal angiofibroma should be included in the differential diagnosis when patients of all ages present with nasal obstruction secondary to a nasal mass, with or without epistaxis.

EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity.

Primary central nervous system lymphoma (PCNSL) is confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. Rarely, PCNSL occurs in the context of immunosuppression (eg, posttransplant lymphoproliferative disorders or HIV [AIDS-related PCNSL]). These cases are poorly characterized, have dismal outcome, and are typically Epstein-Barr virus (EBV)-associated (ie, tissue-positive). We used targeted sequencing and digital multiplex gene expression to compare the genetic landscape and tumor microenvironment (TME) of 91 PCNSL tissues all with diffuse large B-cell lymphoma histology. Forty-seven were EBV tissue-negative: 45 EBV- HIV- PCNSL and 2 EBV- HIV+ PCNSL; and 44 were EBV tissue-positive: 23 EBV+ HIV+ PCNSL and 21 EBV+ HIV- PCNSL. As with prior studies, EBV- HIV- PCNSL had frequent MYD88, CD79B, and PIM1 mutations, and enrichment for the activated B-cell (ABC) cell-of-origin subtype. In contrast, these mutations were absent in all EBV tissue-positive cases and ABC frequency was low. Furthermore, copy number loss in HLA class I/II and antigen-presenting/processing genes were rarely observed, indicating retained antigen presentation. To counter this, EBV+ HIV- PCNSL had a tolerogenic TME with elevated macrophage and immune-checkpoint gene expression, whereas AIDS-related PCNSL had low CD4 gene counts. EBV-associated PCNSL in the immunosuppressed is immunobiologically distinct from EBV- HIV- PCNSL, and, despite expressing an immunogenic virus, retains the ability to present EBV antigens. Results provide a framework for targeted treatment.

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.

Hip fractures are preventable: a proposal for osteoporosis screening and fall prevention in older people.

Osteoporosis is highly prevalent but underdiagnosed and undertreated in Hong Kong. Fragility fractures associated with osteoporosis often result in loss of independence and increased mortality for home-dwelling patients, imposing a high socio-economic burden on society. This issue requires urgent attention given the rapid growth of the elderly population in Hong Kong by approximately 4.3% each year. To address this situation, a group of experts convened to discuss practical ways to reduce the burden of fractures and formulated three recommendations: first, all men (aged ≥70 years) and women (aged ≥65 years) should receive universal dual-energy X-ray absorptiometry assessment for osteoporosis. Second, all men (aged ≥70 years) and women (aged ≥65 years) with a fracture-risk assessment-derived 10-year risk (hip fracture with bone mineral density) ≥3% should receive ≥3 years of anti-osteoporotic treatment. Third, comprehensive structured assessment (including dual-energy X-ray absorptiometry) should be conducted in older patients with a history of falling. By implementing these recommendations, we estimate that we could prevent 5234 hip fractures in 10 years, an annual incidence reduction of approximately 7%, and save HK$425 million in direct medical costs plus substantial indirect savings. Ample clinical and cost-effectiveness data support these recommendations, and studies in Hong Kong and abroad could serve as models on how to implement them. We are confident that by applying these recommendations rigorously and systematically, a significant reduction in hip fractures in Hong Kong is achievable.

Smart Work Injury Management (SWIM) System: Artificial Intelligence in Work Disability Management.

PURPOSE: This paper aims to illustrate an example of how to set up a work injury database: the Smart Work Injury Management (SWIM) system. It is a secure and centralized cloud platform containing a set of management tools for data storage, data analytics, and machine learning. It employs artificial intelligence to perform in-depth analysis via text-mining techniques in order to extract both dynamic and static data from work injury case files. When it is fully developed, this system can provide a more accurate prediction model for cost of work injuries. It can also predict return-to-work (RTW) trajectory and provide advice on medical care and RTW interventions to all RTW stakeholders. The project will comprise three stages. Stage one: to identify human factors in terms of both facilitators and barriers RTW through face-to-face interviews and focus group discussions with different RTW stakeholders in order to collect opinions related to facilitators, barriers, and essential interventions for RTW of injured workers; Stage two: to develop a machine learning model which employs artificial intelligence to perform in-depth analysis. The technologies used will include: 1. Text-mining techniques including English and Chinese work segmentation as well as N-Gram to extract both dynamic and static data from free-style text as well as sociodemographic information from work injury case files; 2. Principle component/independent component analysis to identify features of significant relationships with RTW outcomes or combine raw features into new features; 3. A machine learning model that combines Variational Autoencoder, Long and Short Term Memory, and Neural Turning Machines. Stage two will also include the development of an interactive dashboard and website to query the trained machine learning model. Stage three: to field test the SWIM system. CONCLUSION: SWIM ia secure and centralized cloud platform containing a set of management tools for data storage, data analytics, and machine learning. When it is fully developed, SWIM can provide a more accurate prediction model for the cost of work injuries and advice on medical care and RTW interventions to all RTW stakeholders. ETHICS: The project has been approved by the Ethics Committee for Human Subjects at the Hong Kong Polytechnic University and is funded by the Innovation and Technology Commission (Grant # ITS/249/18FX).

Uterine Fibroid Symptom and Health-related Quality of Life Questionnaire: a Chinese translation and validation study.

INTRODUCTION: The Uterine Fibroid Symptom and Health-related Quality of Life (UFS-QOL) questionnaire is a validated tool in English language to assess treatment outcomes for women with fibroids. We performed a Chinese (traditional) translation and cultural adaptation of it and evaluated its reliability, validity, and responsiveness. METHODS: Overall, 223 Chinese women aged ≥18 years with uterine fibroids self-administered the UFS-QOL, Short-Form Health Survey-12, pictorial blood loss assessment chart (PBAC), and a visual analogue scale (VAS) on fibroid-related symptom severity. Demographics and haemoglobin levels were recorded; physical examination and ultrasound for size of fibroids were performed. Half of the women were followed up 6 months later for responsiveness. RESULTS: Cronbach's alpha coefficients ranged from 0.706 to 0.937, demonstrating high internal reliability. The intra-class correlation coefficients to measure test-retest reliability implied excellent stability of symptom scores (0.819, P<0.001), health-related quality of life scores (0.897, P<0.001), and all subscales (range 0.721-0.870, P<0.001). Convergent validity was demonstrated by positive correlations between the findings of various symptom severity assessment tools (PBAC, VAS on fibroid-related symptoms severity) and the symptom severity domain of Chinese UFS-QOL. In addition, there were positive correlations between health-related quality of life scores of Chinese UFS-QOL and the corresponding subscales of the Short-Form Health Survey-12. Responsiveness was shown by reduction of symptom severity scores and improvement of health-related quality of life scores after treatment. CONCLUSIONS: The Chinese version of the UFS-QOL is valid, reliable, and responsive to changes after treatment.

The covalent binding story of the complement proteins C3 and C4 (I) 1972-1981.

Alex Law and Paul Levine recall their work to establish the covalent bond between C3 and target surfaces. It started with a naive experiment by analyzing the membrane polypeptides of sheep erythrocytes bound with 125I-labelled C3. They found complexes with molecular weight higher than the individual C3 polypeptides. These complexes survived all conditions designed to disrupt non-covalent interactions. They then showed that the bond was an ester, with an active acyl group on C3 which reacted with a hydroxyl group on the acceptor molecule. With the discovery of an internal thioester by Jim Prahl, Jamila Janatova, Brian Tack and their colleagues, it became clear that the reaction was by an acyl transfer from the thioester of C3 to the target hydroxyl group. Later on they showed that C4 also bound covalently to target molecules. By establishing a fluid phase system to study the kinetics of the binding reactions of C3 and C4, Alex was able to continue the work in the MRC Immunochemistry Unit in Oxford from 1981, to eventually determine the chemical mechanism of the binding reaction. In order to give some sense of reality, this article is written as a narrative from Alex, who did the experiments. Both Alex and Paul are retired. Pauls lives on Martha's Vineyard where he writes occasional articles on science for one of the Island's newspapers. Alex lives in Hong Kong and tries to make some sense of the local politics.

Long-term pharyngeal dysphagia after esophagectomy for esophageal cancer-an investigation using videofluoroscopic swallow studies.

Dysphagia is a common symptom of esophageal cancer (EC). Esophagectomy should relieve the presenting dysphagia as the mechanical obstruction caused by the tumor is removed. However, the new onset oropharyngeal dysphagia develops after esophagectomy and the deficit may persist increasing the risk of aspiration pneumonia and mortality as well as adversely affecting quality of life (QOL). This study investigates the persistent swallowing deficits in long-term postesophagectomy patients and explores the factors associated with dysphagia severity, penetration, and aspiration. A better understanding of the swallowing function can aid future management of the condition. A total of 29 patients who were more than six months postesophagectomy for EC, had no history of disease that would likely affect swallowing function or vocal cord palsy underwent detailed videofluoroscopic swallow studies and completed the European Organisation for Research and Treatment of Cancer QLQ-C30 and OES18 QOL questionnaires. Swallowing deficits were analyzed and rated using the videofluoroscopic dysphagia scale (VDS) and the penetration-aspiration scale (PAS). These variables were correlated with the clinical and QOL parameters to determine which factors would affect swallowing function. Our cohort consisted of 27 males and 2 females. The mean duration after esophagectomy when the swallowing study was performed was 3.2 years (range: 0.5-18.4 years). Swallowing deficits were mainly found in the pharyngeal phase of swallowing. The mean total VDS score was 36.1 (SD = 15.2, range: 11.0-69.5) out of a possible 100. The mean PAS score was 4.1 (SD = 2.5, range: 1-8) and 1.5 (SD = 0.9, range: 1-4) for thin and semisolids, respectively. Dysphagia was significantly more severe in males, those of more advanced age at esophagectomy and at swallowing assessment. Increasing pathological N stage significantly correlated with worse PAS score for thin fluid. Self-reports of more pain and less troubles with coughing were also associated with less penetration and aspiration. This study demonstrated that a mild to moderate pharyngeal dysphagia is present late after esophagectomy even in patients without VC palsy or anastomotic stricture. The long-term aspiration rate is comparable to the figures in the literature for those early after esophagectomy. It is suggested that damage to the intercostal nerves and the pulmonary vagus may affect oropharyngeal swallowing function in this population.

Dendritic cells, T cells and their interaction in rheumatoid arthritis.

Dendritic cells (DCs) are the key professional antigen-presenting cells which bridge innate and adaptive immune responses, inducing the priming and differentiation of naive to effector CD4+ T cells, the cross-priming of CD8+ T cells and the promotion of B cell antibody responses. DCs also play a critical role in the maintenance of immune homeostasis and tolerance. DC-T cell interactions underpin the generation of an autoimmune response in rheumatoid arthritis (RA). Here we describe the function of DCs and review evidence for DC and T cell involvement in RA pathogenesis, in particular through the presentation of self-peptide by DCs that triggers differentiation and activation of autoreactive T cells. Finally, we discuss the emerging field of targeting the DC-T cell interaction for antigen-specific immunotherapy of RA.