Repeat resection for recurrent glioblastoma in the temozolomide era: a real-world multi-centre study.

INTRODUCTION: In contrast to standard-of-care treatment of newly diagnosed glioblastoma, there is limited consensus on therapy upon disease progression. The role of resection for recurrent glioblastoma remains unclear. This study aimed to identify factors for overall survival (OS) and post-progression survival (PPS) as well as to validate an existing prediction model. METHODS: This was a multi-centre retrospective study that reviewed consecutive adult patients from 2006 to 2019 that received a repeat resection for recurrent glioblastoma. The primary endpoint was PPS defined as from the date of second surgery until death. RESULTS: 1032 glioblastoma patients were identified and 190 (18%) underwent resection for recurrence. Patients that had second surgery were more likely to be younger (<70 years) (adjusted OR: 0.3; 95% CI: 0.1-0.6), to have non-eloquent region tumours (aOR: 1.7; 95% CI: 1.1-2.6) and received temozolomide chemoradiotherapy (aOR: 0.2; 95% CI: 0.1-0.4). Resection for recurrent tumour was an independent predictor for OS (aOR: 1.5; 95% CI: 1.3-1.7) (mOS: 16.9 months versus 9.8 months). For patients that previously received temozolomide chemoradiotherapy and subsequent repeat resection (137, 13%), the median PPS was 9.0 months (IQR: 5.0-17.5). Independent PPS predictors for this group were a recurrent tumour volume of >50cc (aOR: 0.6; 95% CI: 0.4-0.9), local recurrence (aOR: 1.7; 95% CI: 1.1-3.3) and 5-ALA fluorescence-guided resection during second surgery (aOR: 1.7; 95% CI: 1.1-2.8). A National Institutes of Health Recurrent Glioblastoma Multiforme Scale score of 0 conferred an mPPS of 10.0 months, a score of 1-2, 9.0 months and a score of 3, 4.0 months (log-rank test, p-value < 0.05). CONCLUSION: Surgery for recurrent glioblastoma can be beneficial in selected patients and carries an acceptable morbidity rate. The pattern of recurrence influenced PPS and the NIH Recurrent GBM Scale was a reliable prognostication tool.

Patterns of care and survival of Chinese glioblastoma patients in the temozolomide era: a Hong Kong population-level analysis over a 14-year period.

Background: The aim of this study is to address the paucity of epidemiological data regarding the characteristics, treatment patterns and survival outcomes of Chinese glioblastoma patients. Methods: This was a population-level study of Hong Kong adult (>18 years) Chinese patients with newly diagnosed histologically confirmed glioblastoma between 2006 and 2019. The age standardized incidence rate (ASIR), patient-, tumor- treatment-related characteristics, overall survival (OS) as well as its predictors were determined. Results: One thousand and ten patients with a median follow-up of 10.0 months were reviewed. The ASIR of glioblastoma was 1.0 per 100 000 population with no significant change during the study period. The mean age was 57 + 14 years. The median OS was 10.6 months (IQR: 5.2-18.4). Independent predictors for survival were: Karnofsky performance score >80 (adjusted OR: 0.8; 95% CI: 0.6-0.9), IDH-1 mutant (aOR: 0.7; 95% CI: 0.5-0.9) or MGMT methylated (aOR: 0.7; 95% CI: 0.5-0.8) glioblastomas, gross total resection (aOR: 0.8; 95% CI: 0.5-0.8) and temozolomide chemoradiotherapy (aOR 0.4; 95% CI: 0.3-0.6). Despite the significant increased administration of temozolomide chemoradiotherapy from 39% (127/326) of patients in 2006-2010 to 63% (227/356) in 2015-2019 (P-value < .001), median OS did not improve (2006-2010: 10.3 months vs 2015-2019: 11.8 months) (OR: 1.1; 95% CI: 0.9-1.3). Conclusions: The incidence of glioblastoma in the Chinese general population is low. We charted the development of neuro-oncological care of glioblastoma patients in Hong Kong during the temozolomide era. Although there was an increased adoption of temozolomide chemoradiotherapy, a corresponding improvement in survival was not observed.

Correlation of urodynamic studies and somatosensory evoked potential and their prognostic value in children with closed spinal dysraphism.

INTRODUCTION: Somatosensory evoked potential (SSEP) and urodynamic studies (UD) are valuable tools for assessing patients with closed spinal dysraphism (CSD) before neurosurgical intervention. No studies have correlated their findings in this cohort and our aim is to study their correlation and prognostic value in pediatric patients with closed spinal dysraphism. METHODS: Retrospective review of all patients referred to a multidisciplinary clinic in a tertiary pediatric surgical center over a 17 years period between April 2004 to September 2021 was performed. Inclusion criteria were <18 years old, diagnosed with CSD, with SSEP and UD done within 1 year of each other. Demographics data collected include age at presentation/at referral/at neurosurgical operation, gender, symptoms at presentation and intra-operative diagnoses. Pre-operative SSEP and UD findings were documented. Primary outcome was UD results in the group with normal and abnormal SSEP. Secondary outcome was urological and bowel function outcome in 4 groups of patients (Group A-both normal SSEP and UD, Group B- abnormal SSEP only, Group C - abnormal UD only and Group D-both abnormal SSEP and UD). RESULTS: A total of 45 patients were included for analysis. Mean follow up time was 118.9 months (24-216 months, SD 55.8 months). SSEP was normal in 20 patients and abnormal in 25 patients. Baseline demographics, preoperative symptoms and imaging were similar between 2 groups. Primary outcome Patients with abnormal SSEP were more likely to have abnormal UD results with a statistically significant difference (84% vs 40%, p < 0.05). They have a significantly higher end-fill detrusor pressure (12% vs 0%, p < 0.05), abnormal bladder compliance (20% vs 0%, p < 0.05), abnormal cystometric capacity (48% vs 10%, p < 0.05), poor emptying efficiency (24% vs 5%, p < 0.05) and sphincter incompetence (8% vs 0%, p < 0.05). Secondary outcome When compared to Groups A to C, patients in group D were more likely to be on anti-cholinergic (33.3% vs 4.3%, p < 0.05), required clean intermittent catheterization (42.9% vs 4.3%, p < 0.05) and had intravesical botulinum injection (19% vs 0%, p < 0.05). All the patients who had augmentation cystoplasty were in this group as well. Bowel function in terms of regular enema use was also statistically significantly higher in this group (33.4% p < 0.05). CONCLUSION: Pre-operative SSEP and UD results correlate well in patients with closed spinal dysraphism. Patients with abnormal SSEP and UD preoperatively have higher risk of urological deterioration over time. Close monitoring in this group is warranted.

Radioactive iodine dose and survival in cats with hyperthyroidism (2015-2020).

OBJECTIVES: Radioactive iodine (131I) is the preferred treatment for feline hyperthyroidism but neither the optimal 131I dose nor consistent predictors of post-treatment azotaemia have been determined. The aims of the study were to evaluate the relationships between: (1) 131I dose and survival; and (2) pretreatment and post-treatment serum creatinine concentration. METHODS: Medical records of hyperthyroid cats treated with 131I at a single referral hospital were reviewed. Information regarding signalment, body weight, pretreatment and post-treatment serum total thyroxine concentration (TT4), serum creatinine concentration, 131I dose and survival were determined. Multivariable Cox proportional hazards analysis was used to identify variables associated with survival. Multivariable linear regression analysis was used to identify variables associated with post-treatment serum creatinine concentration. RESULTS: One hundred and ninety-eight (79 male, 119 female) cats were treated for hyperthyroidism with 131I (median dose 138 MBq; interquartile range 92-168). Median survival time was 1153 days (range 16-1871). Post-treatment serum creatinine (P <0.001) and age (P = 0.049) were significantly associated with survival. Every 10 µmol/l increase in post-treatment serum creatinine concentration and every year increase in age was associated with a 1.07-fold (confidence interval [CI] 1.04-1.11) and 1.17-fold (CI 1.00-1.37) increase in the daily hazard of death, respectively. Pretreatment serum creatinine concentration was directly, and post-treatment serum TT4 concentration was inversely, associated with post-treatment serum creatinine concentration. Every 1 µmol/l increase in pretreatment serum creatinine concentration was associated with an increase in post-treatment serum creatinine concentration of 0.7 µmol/l (SE 0.17; P <0.001). Conversely, every 1 nmol/l decrease in post-treatment serum TT4 concentration was associated with a 1.2 µmol/l (SE 0.61; P <0.001) increase in post-treatment serum creatinine concentration. CONCLUSIONS AND RELEVANCE: Post-treatment serum TT4 concentration was associated with post-treatment azotaemia, which was associated with survival. Although 131I dose was not directly associated with survival, dosing strategies that minimise post-treatment hypothyroidism and azotaemia could improve patient survival.

Progressive increases in creatine kinase activity in an anorexic cat with necrotising myopathy.

CASE SUMMARY: A 5-year-old castrated male domestic shorthair cat with weight loss and reduced appetite was evaluated for increased and progressively rising creatine kinase (CK) activity. The cat had recently been diagnosed with hepatic lipidosis. Muscle biopsy and histopathology revealed mild myonecrosis and phagocytosis without obvious inflammatory cell infiltrates. Resolution of necrotising myopathy was observed after a short course of anti-inflammatory prednisolone and nutritional supplementation. RELEVANCE AND NOVEL INFORMATION: This is the first report of a necrotising myopathy in a cat associated with progressively increasing CK activity and decreased appetite. Anorexia in cats has been associated with increased CK activity, but an underlying cause of this CK elevation has only been postulated. Here we document muscle necrosis and muscle stiffness in a cat with anorexia.

Validation of the traditional script Chinese version of the brief negative symptom scale.

Negative symptoms are a core feature of schizophrenia and account for much of the long-term morbidity and poor functional outcome of people with schizophrenia. The Brief Negative Symptom Scale (BNSS) was developed to address the main limitations of the existing scales for the assessment of negative symptoms. The BNSS has been translated into Italian, Spanish, German, Turkish and simplified Chinese versions with excellent psychometric properties. In this study, a Chinese (traditional script) version of the Brief Negative Symptom Scale (C-BNSS) was developed and validated to facilitate future research on the Chinese population in Hong Kong. Psychometric properties were examined in 149 individuals with schizophrenia. The C-BNSS showed excellent internal consistency (α = 0.96), high inter-rater reliability (intra-class correlation = 0.98), and high test-retest reliability (Spearman's r = 0.96). Convergent validity was supported by high correlations between C-BNSS total score and subscales with the Scale for Assessment of Negative Symptoms (SANS), Negative Symptom subscale of the Positive and Negative Syndrome Scale (PANSS), and Global Assessment of Functioning (GAF) score. Discriminant validity was supported by low correlations between the C-BNSS total score and the PANSS positive subscale, Calgary Depression Scale, and Simpson-Angus Scale for extrapyramidal symptoms. The C-BNSS showed a five- factor structure on Confirmatory Factor Analysis (CFA), confirming findings of previous studies. Findings indicate that the C-BNSS demonstrates excellent psychometric properties, which are comparable to the original English version. It is a promising instrument for use in clinical trials as well as in clinical practice.

A Design Study Investigating Augmented Reality and Photograph Annotation in a Digitalized Grossing Workstation.

CONTEXT: Within digital pathology, digitalization of the grossing procedure has been relatively underexplored in comparison to digitalization of pathology slides. AIMS: Our investigation focuses on the interaction design of an augmented reality gross pathology workstation and refining the interface so that information and visualizations are easily recorded and displayed in a thoughtful view. SETTINGS AND DESIGN: The work in this project occurred in two phases: the first phase focused on implementation of an augmented reality grossing workstation prototype while the second phase focused on the implementation of an incremental prototype in parallel with a deeper design study. SUBJECTS AND METHODS: Our research institute focused on an experimental and "designerly" approach to create a digital gross pathology prototype as opposed to focusing on developing a system for immediate clinical deployment. STATISTICAL ANALYSIS USED: Evaluation has not been limited to user tests and interviews, but rather key insights were uncovered through design methods such as "rapid ethnography" and "conversation with materials". RESULTS: We developed an augmented reality enhanced digital grossing station prototype to assist pathology technicians in capturing data during examination. The prototype uses a magnetically tracked scalpel to annotate planned cuts and dimensions onto photographs taken of the work surface. This article focuses on the use of qualitative design methods to evaluate and refine the prototype. Our aims were to build on the strengths of the prototype's technology, improve the ergonomics of the digital/physical workstation by considering numerous alternative design directions, and to consider the effects of digitalization on personnel and the pathology diagnostics information flow from a wider perspective. A proposed interface design allows the pathology technician to place images in relation to its orientation, annotate directly on the image, and create linked information. CONCLUSIONS: The augmented reality magnetically tracked scalpel reduces tool switching though limitations in today's augmented reality technology fall short of creating an ideal immersive workflow by requiring the use of a monitor. While this technology catches up, we recommend focusing efforts on enabling the easy creation of layered, complex reports, linking, and viewing information across systems. Reflecting upon our results, we argue for digitalization to focus not only on how to record increasing amounts of data but also how these data can be accessed in a more thoughtful way that draws upon the expertise and creativity of pathology professionals using the systems.

Injectable thermosensitive gelling delivery system for the sustained release of lidocaine.

BACKGROUND: Patients undergoing arthroplasty require appropriate postsurgical pain relief. Analgesia is typically achieved through bolus doses of short-acting local anesthetics and with oral analgesics such as opiates, which are associated with systemic side effects. By formulating an injectable thermosensitive gelling system containing lidocaine, sustained and local delivery can be achieved following a single administration. RESULTS: Poloxamer-based thermosensitive gelling formulations were prepared. Altering the weight ratios of poloxamers affected the sol-to-gel transition temperature, mechanical and rheological properties and in vitro drug release. Desirable formulations gelled between 28 and 33°C providing sustained release of lidocaine over 48 h. CONCLUSION: Thermosensitive gelling systems are promising for sustained drug release following patient administration and may be beneficial in addressing postoperative pain.

Activation of eosinophils interacting with dermal fibroblasts by pruritogenic cytokine IL-31 and alarmin IL-33: implications in atopic dermatitis.

BACKGROUND: IL-31 is a pruritogenic cytokine, and IL-33 is an alarmin for damaging inflammation. They together relate to the pathogenesis of atopic dermatitis (AD). Eosinophil infiltration into the inner dermal compartment is a predominant pathological feature of AD. We herein investigated the in vitro inflammatory effects of IL-31 and IL-33 on the activation of human eosinophils and dermal fibroblasts. METHODOLOGY/PRINCIPAL FINDINGS: Receptors, adhesion molecules and signaling molecules were assessed by Western blot or flow cytometry. Chemokines and cytokine were quantitated by multiplex assay. Functional IL-31 receptor component IL-31RA, OSMR-ß and IL-33 receptor component ST2 were constitutively expressed on the surface of eosinophils. Co-culture of eosinophils and fibroblasts significantly induced pro-inflammatory cytokine IL-6 and AD-related chemokines CXCL1, CXCL10, CCL2 and CCL5. Such inductions were further enhanced with IL-31 and IL-33 stimulation. IL-31 and IL-33 could significantly provoke the release of CXCL8 from eosinophils and fibroblasts, respectively, which was further enhanced upon co-culture. In co-culture, eosinophils and fibroblasts were the main source for the release of CCL5, and IL-6, CXCL1, CXCL8, CXCL10 and CCL2, respectively. Direct interaction between eosinophils and fibroblasts was required for CXCL1, CXCL10, CXCL8 and CCL5 release. Cell surface expression of intercellular adhesion molecule-1 on eosinophils and fibroblasts was up-regulated in co-culture upon IL-31 and IL-33 stimulation. The interaction between eosinophils and fibroblasts under IL-31 and IL-33 stimulation differentially activated extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, nuclear factor-κB and phosphatidylinositol 3-kinase-Akt pathways. Using specific signaling molecule inhibitors, the differential induction of IL-31 and IL-33-mediated release of cytokines and chemokines such as IL-6 and CXCL8 from co-culture should be related to their distinct activation profile of intracellular signaling pathways. CONCLUSIONS/SIGNIFICANCE: The above findings suggest a crucial immunopathological role of IL-31 and IL-33 in AD through the activation of eosinophils-fibroblasts interaction via differential intracellular signaling mechanisms.

Intracellular signaling mechanisms regulating the activation of human eosinophils by the novel Th2 cytokine IL-33: implications for allergic inflammation.

The novel interleukin (IL)-1 family cytokine IL-33 has been shown to activate T helper 2 (Th2) lymphocytes, mast cells and basophils to produce an array of proinflammatory cytokines, as well as to mediate blood eosinophilia, IgE secretion and hypertrophy of airway epithelium in mice. In the present study, we characterized the activation of human eosinophils by IL-33, and investigated the underlying intracellular signaling mechanisms. IL-33 markedly enhanced eosinophil survival and upregulated cell surface expression of the adhesion molecule intercellular adhesion molecule (ICAM)-1 on eosinophils, but it suppressed that of ICAM-3 and L-selectin. In addition, IL-33 mediates significant release of the proinflammatory cytokine IL-6 and the chemokines CXCL8 and CCL2. We found that IL-33-mediated enhancement of survival, induction of adhesion molecules, and release of cytokines and chemokines were differentially regulated by activation of the nuclear factor (NF)-kappaB, p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) pathways. Furthermore, we compared the above IL-33 activities with two structurally and functionally related cytokines, IL-1beta and IL-18. IL-1beta, but not IL-18, markedly upregulated cell surface expression of ICAM-1. IL-1beta and IL-18 also significantly enhanced eosinophil survival, and induced the release of IL-6 and chemokines CXCL8 and CCL2 via the activation of the NF-kappaB, p38 MAPK and ERK pathways. Synergistic effects on the release of IL-6 were also observed in combined treatment with IL-1beta, IL-18 and IL-33. Taken together, our findings provide insight into IL-33-mediated activation of eosinophils via differential intracellular signaling cascades in the immunopathogenesis of allergic inflammation.

Airway inflammatory and spirometric measurements in obese children.

OBJECTIVES: To investigate the association between obesity and airway inflammation and spirometric parameters in local children. DESIGN: Cross-sectional and observational study. SETTING: Paediatric clinics of a university-affiliated teaching hospital in Hong Kong. PATIENTS: Chinese subjects aged 6 to 18 years were recruited from the paediatric clinics. Obesity was defined as being 120% or more of the median weight-for-height. MAIN OUTCOME MEASURES: Airway inflammation assessed by exhaled nitric oxide concentration; lung function evaluated by measuring forced expiratory flow in 1-second and forced vital capacity using spirometry; and peak expiratory flow rate measured by using a mini-Wright peak flow meter. RESULTS: Fifty-five subjects were recruited into four groups as follows: 13 non-obese controls, 16 obese non-asthmatics, 15 non-obese asthmatics, and 11 obese asthmatics. The median (interquartile range) exhaled nitric oxide concentrations of these groups were 17.6 (14.4-20.9), 33.3 (26.1-75.4), 65.7 (32.0-110.0) and 49.2 (41.1-82.6) parts per billion, respectively (P=0.001 for trend). Post-hoc analysis revealed higher exhaled nitric oxide concentration in the latter three groups (obese and/or asthmatic subjects) than controls (P< or =0.002). Exhaled nitric oxide concentration did not differ among obese non-asthmatics, non-obese asthmatics, and obese asthmatics (P>0.1 for all). In non-asthmatics, exhaled nitric oxide concentration correlated positively with age (P=0.048), weight-for-height z-score (P=0.001), and forced vital capacity (P=0.009). Weight-for-height z-score correlated positively with forced vital capacity (P=0.041), but inversely with the forced expiratory flow in 1-second/forced vital capacity ratio (P=0.049). Such correlations were not observed in asthmatic children. CONCLUSION: Increased airway inflammation as revealed by exhaled nitric oxide concentration was found in obese non-asthmatic children. Weight-for-height z-score as an indicator of childhood obesity correlated with exhaled nitric oxide concentration and spirometric parameters in children without asthma. Nonetheless, concomitant obesity does not influence exhaled nitric oxide concentration in asthmatic children. Further studies are needed to identify the pathophysiologic mechanisms for such associations.

Perceived parental control and psychological well-being in Chinese adolescents in Hong Kong.

Chinese secondary school students (N=2,758) responded to measures of perceived parental behavioral control (parental knowledge, expectation, monitoring, discipline and demandingness), parental psychological control, and adolescent psychological well-being (hopelessness, mastery, life satisfaction and self-esteem). Results showed that composite parental behavioral control was weakly related to parental psychological control, whereas discrete aspects of parental behavioral control were differentially related to parental psychological control. Although parental psychological control was negatively related to adolescent psychological well-being, parental behavioral control was positively related to adolescent adjustment. The present findings underscore the role of parental control in the psychological well-being of Chinese adolescents at Secondary 2 level in Hong Kong. The implications of the findings for the development of positive youth development programs in Hong Kong are discussed.

Development of a positive youth development program: promoting the mental health of stressful adolescents using principles of Problem Solving Therapy.

This paper outlines the proposal for the development, implementation, and evaluation of a positive youth development program that attempts to promote the mental health of stressful Chinese adolescents using principles of Problem Solving Therapy (PST). There are two general aims of PST: to help clients identify life difficulties and resolve them, as well as to teach them skills on how to deal with future problems. The proposed project will utilize the principles of PST as the guiding framework to run two mental health promotion courses for adolescents who are experiencing disturbing stressful responses and students who want to improve their stress management style. Both objective and subjective outcome evaluation strategies will be carried out to assess the effectiveness of the intervention to promote the psychological well-being in adolescents who are experiencing stress. A related sample proposal is described that can give social workers some insight on how to prepare a proposal for developing the Tier 2 Program of the Project PATHS (Positive Adolescent Training through Holistic Social Programs).

Trends in adolescent suicide in Hong Kong for the period 1980 to 2003.

This paper utilizes existing statistics on adolescent suicide to examine adolescent suicide trends and patterns in Hong Kong for the period 1980 to 2003. Several trends and patterns could be revealed from the analyses. First, there was a gradual rising trend where adolescent suicide rates in the 1990s and the early 2000s were higher than those in the 1980s. Second, suicide rates for adolescents aged 10-24 years were lower than those of other adult age groups. Third, although adolescent suicide rates in Hong Kong were lower than those reported in some English-speaking countries and Mainland China, the figures were higher than those reported in Taiwan. Fourth, suicide rates among teenagers in early adolescence were lower than those among adolescents in late adolescence. Fifth, although male adolescent suicide rates were in general higher than female adolescent suicide rates (10-24 age group), gender differences in suicide rates appeared to be moderated by age. Sixth, there was a gradual rising trend in adolescent proportional mortality rates for suicide since the 1990s. Seventh, proportional mortality rates for suicide among teenagers in early adolescence were lower than those among adolescents in late adolescence. Finally, although jumping from a height was a common method of adolescent suicide, there was a rising trend of using other methods, such as taking drugs, hanging and charcoal burning. The observed adolescent suicide phenomena are discussed in this study with reference to the socio-cultural context of Hong Kong.