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.

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.

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).

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.

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.

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.

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 value of neck drain in esophageal surgery: a randomized trial.

The use of surgical drains in certain clean elective operations remains controversial. To evaluate the role of closed-suction drain for an esophageal anastomosis in the neck, we conducted a randomized, controlled study in 40 patients with esophageal carcinoma who underwent esophagectomy with an esophageal anastomosis in the neck, half of whom had a neck drain inserted at the end of operation. The median (range) duration of drainage was 46 hours (36 to 88 hours). The median (range) amount of drainage was 63 ml (15 to 210 ml). There was no incidence of haematoma or seroma formation in both the drained and non-drained groups. Anastomotic leakage did not occur in any patient. The benefits of closed suction neck drain could not be demonstrated. Routine use of neck drain for esophageal anastomosis in the neck is not necessary.

Appropriate timing for surgery after neoadjuvant chemoradiation for esophageal cancer.

Optimal interval between neoadjuvant chemoradiotherapy (CRT) and surgery is not elucidated for esophageal squamous carcinoma. The aim of this study is to evaluate the impact of this time interval on patient outcome. Patients treated with neoadjuvant CRT followed by surgery between 2002 and 2009 were analyzed. Patients were divided into two groups based on the median interval to surgery (64 days): A  64 days (n = 53). A second analysis was performed by re-classifying patients into three interval groups: A* ≤ 40 days (n = 16); B* 41-80 days (n = 60); C* > 80 days (n = 31). Operative outcome, pathological data, and long-term survival were analyzed. One hundred and seven (n = 107) patients were analyzed. Five patients (9.4%) in group B had an anastomotic leak compared with no leakage from group A (P < 0.021). The complete pathological response was comparable in groups A and B (35% vs. 24.5%, p = 0.23). R0 was significantly lower in group A* (A*: 56.3%, B*: 90%, C*: 74.2%, P = 0.006). In patients with R0 resection, 5-year survival was significantly better in group A than B (71.7% vs. 51%, P = 0.032) and in group A* (A* 100% vs. B* 60.2% & C* 48.3%; A* vs. B*, P = 0.036; A* vs. C*, P = 0.019). Complete pathological response was an independent predictor of survival. Early surgery with R0 resection following neoadjuvant CRT may lead to a better outcome. Further prospective studies are still necessary to provide better insight into the issue. At present, timing of surgery should be individualized and performed at the earliest opportunity.

Outcomes after oesophageal perforation: a retrospective cohort study of patients with different aetiologies.

INTRODUCTION: The mortality rate after oesophageal perforation is high despite advances in operative and non-operative techniques. In this study, we sought to identify risk factors for hospital mortality after oesophageal perforation treatment. METHODS: We retrospectively examined patients treated for oesophageal perforation in a university teaching hospital in Hong Kong between January 1997 and December 2013. Their demographic and clinical characteristics, aetiology, management strategies, and outcomes were recorded and analysed. RESULTS: We identified a cohort of 43 patients treated for perforation of the oesophagus (28 men; median age, 66 years; age range, 30-98 years). Perforation was spontaneous in 22 (51.2%) patients (15 with Boerhaave's syndrome and seven with malignant perforation), iatrogenic in 15 (34.9%), and provoked by foreign body ingestion in six (14.0%). Of the patients, 14 (32.6%) had pre-existing oesophageal disease. Perforation occurred in the intrathoracic oesophagus in 30 (69.8%) patients. Emergent surgery was undertaken in 23 patients: 16 underwent primary repair, six surgical drainage or exclusion, and one oesophagectomy. Twenty patients were managed non-operatively, 13 of whom underwent stenting. Two stented patients subsequently required oesophagectomy. Four patients had clinical signs of leak after primary repair: two were treated conservatively and two required oesophagectomy. Overall, six (14.0%) patients required oesophagectomy, one of whom died. Nine other patients also died in hospital; the hospital mortality rate was 23.3%. Pre-existing pulmonary and hepatic disease, and perforation associated with malignancy were significantly associated with hospital mortality (P=0.03, <0.01, and <0.01, respectively). CONCLUSIONS: Most oesophageal perforations were spontaneous. Mortality was substantial despite modern therapies. Presence of pre-existing pulmonary disease, hepatic disease, and perforation associated with malignancy were significantly associated with hospital mortality. Salvage oesophagectomy was successful in selected patients.

Single-material semiconductor hyperbolic metamaterials.

Layered semiconductor hyperbolic metamaterials for the mid-infrared are grown by molecular beam epitaxy using a single material system, doped and undoped InAs. The onset wavelength for metamaterial behavior can be tuned from 5.8µm to beyond 10µm, while the fill factor ranges from 0.25 to 0.75, resulting in designer optical behavior. The reflection and transmission behavior were studied by Fourier transform spectroscopy and modeled using effective medium theory. We also conducted a geometric optics experiment to demonstrate negative refraction of our materials.

Hypoxia-induced changes to integrin α 3 glycosylation facilitate invasion in epidermoid carcinoma cell line A431.

Hypoxia is a critical microenvironmental factor that drives cancer progression through angiogenesis and metastasis. Glycoproteins, especially those on the plasma membrane, orchestrate this process; however, questions remain regarding hypoxia-perturbed protein glycosylation in cancer cells. We focused on the effects of hypoxia on the integrin family of glycoproteins, which are central to the cellular processes of attachment and migration and have been linked with cancer in humans. We employed electrostatic repulsion hydrophilic interaction chromatography coupled with iTRAQ labeling and LC-MS/MS to identify and quantify glycoproteins expressed in A431. The results revealed that independent of the protein-level change, N-glycosylation modifications of integrin α 3 (ITGA3) were inhibited by hypoxia, unlike in other integrin subunits. A combination of Western blot, flow cytometry, and cell staining assays showed that hypoxia-induced alterations to the glycosylation of ITGA3 prevented its efficient translocation to the plasma membrane. Mutagenesis studies demonstrated that simultaneous mutation of glycosites 6 and 7 of ITGA3 prevented its accumulation at the K562 cell surface, which blocked integrin α 3 and ß 1 heterodimer formation and thus abolished ITGA3's interaction with extracellular ligands. By generating A431 cells stably expressing ITGA3 mutated at glycosites 6 and 7, we showed that lower levels of ITGA3 on the cell surface, as induced by hypoxia, conferred an increased invasive ability to cancer cells in vitro under hypoxic conditions. Taken together, these results revealed that ITGA3 translocation to the plasma membrane suppressed by hypoxia through inhibition of glycosylation facilitated cell invasion in A431.

Spontaneous circumferential intramural esophageal dissection complicated with esophageal perforation and esophageal-pleural fistula: a case report and literature review.

Spontaneous intramural esophageal dissection (IED) is a rare disease entity. There are few reports of spontaneous IED requiring surgical treatment. Hereby, we report a 37-year-old gentleman who was diagnosed to have spontaneous extensive circumferential IED complicated with esophageal perforation, empyema, and esophageal-pleural fistula. Esophageal stenting and drainage of empyema were unsuccessful. Computed tomography and gastrografin contrast swallow demonstrated a leak to the pleural cavity, suggestive of esophageal-pleural fistula. Subsequently, a two-stage operation was performed: cervical esophagogastrostomy to bypass the perforated esophagus, followed by esophagectomy and decortication of the right lung. The patient recovered and was discharged home after a 3-week hospitalization. The management principles and recent published literature related to IED were reviewed.

Worldwide Esophageal Cancer Collaboration: pathologic staging data.

We report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for patients with pathologically staged cancer of the esophagus and esophagogastric junction after resection or ablation with no preoperative therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted de-identified data using standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 13,300 patients, 5,631 had squamous cell carcinoma, 7,558 adenocarcinoma, 85 adenosquamous carcinoma, and 26 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (51%), little weight loss (1.8 kg), 0-2 ECOG performance status (83%), and a history of smoking (70%). Cancers were pT1 (24%), pT2 (15%), pT3 (50%), pN0 (52%), pM0 (93%), and pG2-G3 (78%); most involved distal esophagus (71%). Non-risk-adjusted survival for both squamous cell carcinoma and adenocarcinoma was monotonic and distinctive across pTNM. Survival was more distinctive for adenocarcinoma than squamous cell carcinoma when pT was ordered by pN. Survival for pTis-1 adenocarcinoma was better than for squamous cell carcinoma, although monotonic and distinctive for both. WECC pathologic staging data is improved over that of the 7th edition, with more patients studied and patient and cancer variables collected. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics, and should direct 9th edition data collection. However, the role of pure pathologic staging as the principal point of reference for esophageal cancer staging is waning.

Worldwide Esophageal Cancer Collaboration: clinical staging data.

To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection.

Worldwide Esophageal Cancer Collaboration: neoadjuvant pathologic staging data.

To address uncertainty of whether pathologic stage groupings after neoadjuvant therapy (ypTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for pathologically staged cancers after neoadjuvant therapy from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 7,773 pathologically staged neoadjuvant patients, 2,045 had squamous cell carcinoma, 5,686 adenocarcinoma, 31 adenosquamous carcinoma, and 11 undifferentiated carcinoma. Patients were older (61 years) men (83%) with normal (40%) or overweight (35%) body mass index, 0-1 Eastern Cooperative Oncology Group performance status (96%), and a history of smoking (69%). Cancers were ypT0 (20%), ypT1 (13%), ypT2 (18%), ypT3 (44%), ypN0 (55%), ypM0 (94%), and G2-G3 (72%); most involved the distal esophagus (80%). Non-risk-adjusted survival for yp categories was unequally depressed, more for earlier categories than later, compared with equivalent categories from prior WECC data for esophagectomy-alone patients. Thus, survival of patients with ypT0-2N0M0 cancers was intermediate and similar regardless of ypT; survival for ypN+ cancers was poor. Because prognoses for ypTNM and pTNM categories are dissimilar, prognostication should be based on separate ypTNM categories and groupings. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient, cancer, and treatment characteristics and should direct 9th edition data collection.

Opioid therapy for chronic non-cancer pain: guidelines for Hong Kong.

Opioids are increasingly used to control chronic non-cancer pain globally. International opioid guidelines have been issued in many different countries but a similar document is not generally available in Hong Kong. Chronic opioid therapy has a role in multidisciplinary management of chronic non-cancer pain despite insufficient evidence for its effectiveness and safety for long-term use. This document reviews the current literature to inform Hong Kong practitioners about the rational use of chronic opioid therapy in chronic non-cancer pain. It also aims to provide useful recommendations for the appropriate, effective, and safe use of such therapy in the management of chronic non-cancer pain in adults. Physicians should conduct a comprehensive biopsychosocial evaluation of patients prior to the commencement of opioid therapy. When opioid use is deemed appropriate, the patient should provide informed consent within an agreement that specifies treatment goals and expectations. A trial of opioid can be commenced and, provided there is progress towards treatment goals, then chronic therapy can be considered at a dose that minimises harm. Monitoring of effectiveness, safety, and drug misuse should be continued. Treatment should be stopped when opioids become ineffective, intolerable, or misused. The driving principles for opioid prescription in chronic pain management should be: start with a low dose, titrate slowly, and maintain within the shortest possible time.