Clinical features and outcome of retinoblastoma at the Vietnam National Cancer Hospital.

OBJECTIVES: To characterize the clinical features, treatment, and outcome of children diagnosed with retinoblastoma (RB) at Vietnam National Cancer Hospital. METHODS: The study enrolled all RB patients newly diagnosed at Vietnam National Cancer Hospital from January 2018 to December 2022. The primary endpoint was overall survival (OS) and the eye salvage rate. RESULTS: In total, 139 patients were enrolled, 51.8% patients were male. Median age was 18.9 months. Most patients presented with leukocoria (63.3%), followed by strabismus (14.4%), and 43.9% had bilateral disease. Of 200 eyes, 129 (64.5%) were classified as group E. Extraocular extension was noted in 10 of 139 patients (7.2%). About one-third of the patients lived more than 300 kilometers (km) away from these hospitals, and 17.3% of the patients belonged to minority groups, both of which were dominated by group E and extraocular or high-risk eyes at the time of consultation. Primary enucleation was done for 57 eyes (28.5%), and 51 of 61 patients (83.6%) received eye salvage therapy in bilateral RB group. At study closure, 127 children were alive at the last follow-up, 12 cases were confirmed dead. The 5-year OS and progression-free survival (PFS) rates were 90.3% and 85.9%, respectively. In particular, ethnic minority, distance to hospital more than 150 km, and extraocular disease were significantly associated with higher mortality among children with RB treated in Vietnam National Cancer Hospital. CONCLUSIONS: There is a need to support for screening RB with early symptoms in grassroots medical facilities and raise awareness among patients' families through health education programs. Besides, caring and supporting treatment for patients from the ethnic minority and who live far from hospitals are also extremely necessary.

Consensus recommendations for the screening, diagnosis, and management of Helicobacter pylori infection in Hong Kong.

Helicobacter pylori infection causes chronic gastric inflammation that contributes to various gastroduodenal diseases, including peptic ulcer and gastric cancer. Despite broad regional variations, the prevalence of resistance to antibiotics used to manage H pylori infection is increasing worldwide; this trend could hinder the success of eradication therapy. To increase awareness of H pylori and improve the diagnosis and treatment of its infection in Hong Kong, our consensus panel proposed a set of guidance statements for disease management. We conducted a comprehensive review of literature published during 2011 and 2021, with a focus on articles from Hong Kong or other regions of China. We evaluated the evidence using the Oxford Centre for Evidence-Based Medicine's 2011 Levels of Evidence and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system and sought consensus through online voting and a subsequent face-to-face meeting, which enabled us to develop and refine the guidance statements. This report consists of 24 statements regarding the epidemiology and burden, screening and diagnosis, and treatment of H pylori. Key guidance statements include a recommendation to use the test-and-treat approach for high-risk individuals, as well as the confirmation that triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin remains a valid first-line option for adults and children in Hong Kong.

Physical properties of root cementum: Part 28. Effects of high and low water fluoridation on orthodontic root resorption: A microcomputed tomography study.

INTRODUCTION: Transient inflammatory surface resorption, referred to as orthodontic induced inflammatory root resorption (OIIRR), is an iatrogenic consequence of orthodontic tooth movement. Systemic fluoride has been associated with a reduction of OIIRR. This study aimed to investigate the effects of water fluoridation levels on OIIRR in a clinically applicable human orthodontic model. METHODS: Twenty-eight patients who required bilateral maxillary first premolar extraction as part of orthodontic treatment were selected from 2 cities with high and low water fluoridation of ≥2 ppm and ≤0.05 ppm, respectively. Patients were separated into high fluoride (HF) and low fluoride (LF) groups on the basis of water fluoridation levels. Bilateral maxillary first premolar teeth were subjected to 150 g of buccal tipping forces for 12 weeks with reactivation every 4 weeks. Teeth were extracted at the end of 12 weeks. Root resorption crater volume was determined using microcomputed tomography and 3-dimensional reconstruction. RESULTS: HF group showed significantly less mean root resorption volume on the palatal root surface when compared with the LF group (P = 0.025). This difference was specifically displayed at palatal apical regions (P = 0.041). When root resorption volumes from the zones of orthodontic pressure (buccal cervical, palatal apical) were combined, the mean difference between HF and LF groups was statistically significant (P = 0.045). CONCLUSIONS: Findings of the present study indicated a positive correlation between water fluoridation and the reduction of OIIRR, especially at the zones of orthodontic pressure, using a clinically relevant human orthodontic model.

Erythrocytes identify complement activation in patients with COVID-19.

COVID-19, the disease caused by the SARS-CoV-2 virus, can progress to multisystem organ failure and viral sepsis characterized by respiratory failure, arrhythmias, thromboembolic complications, and shock with high mortality. Autopsy and preclinical evidence implicate aberrant complement activation in endothelial injury and organ failure. Erythrocytes express complement receptors and are capable of binding immune complexes; therefore, we investigated complement activation in patients with COVID-19 using erythrocytes as a tool to diagnose complement activation. We discovered enhanced C3b and C4d deposition on erythrocytes in COVID-19 sepsis patients and non-COVID sepsis patients compared with healthy controls, supporting the role of complement in sepsis-associated organ injury. Our data suggest that erythrocytes may contribute to a precision medicine approach to sepsis and have diagnostic value in monitoring complement dysregulation in COVID-19-sepsis and non-COVID sepsis and identifying patients who may benefit from complement targeted therapies.

Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE.

BACKGROUND: In the KATHERINE study (NCT01772472), patients with residual invasive early breast cancer (EBC) after neoadjuvant chemotherapy (NACT) plus human epidermal growth factor receptor 2 (HER2)-targeted therapy had a 50% reduction in risk of recurrence or death with adjuvant trastuzumab emtansine (T-DM1) versus trastuzumab. Here, we present additional exploratory safety and efficacy analyses. PATIENTS AND METHODS: KATHERINE enrolled HER2-positive EBC patients with residual invasive disease in the breast/axilla at surgery after NACT containing a taxane (± anthracycline, ± platinum) and trastuzumab (± pertuzumab). Patients were randomized to adjuvant T-DM1 (n = 743) or trastuzumab (n = 743) for 14 cycles. The primary endpoint was invasive disease-free survival (IDFS). RESULTS: The incidence of peripheral neuropathy (PN) was similar regardless of neoadjuvant taxane type. Irrespective of treatment arm, baseline PN was associated with longer PN duration (median, 105-109 days longer) and lower resolution rate (∼65% versus ∼82%). Prior platinum therapy was associated with more grade 3-4 thrombocytopenia in the T-DM1 arm (13.5% versus 3.8%), but there was no grade ≥3 hemorrhage in these patients. Risk of recurrence or death was decreased with T-DM1 versus trastuzumab in patients who received anthracycline-based NACT [hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.38-0.67], non-anthracycline-based NACT (HR = 0.43; 95% CI: 0.22-0.82), presented with cT1, cN0 tumors (0 versus 6 IDFS events), or had particularly high-risk tumors (HRs ranged from 0.43 to 0.72). The central nervous system (CNS) was more often the site of first recurrence in the T-DM1 arm (5.9% versus 4.3%), but T-DM1 was not associated with a difference in overall risk of CNS recurrence. CONCLUSIONS: T-DM1 provides clinical benefit across patient subgroups, including small tumors and particularly high-risk tumors and does not increase the overall risk of CNS recurrence. NACT type had a minimal impact on safety.

Effects of rapid and slow maxillary expansion on root resorption: a micro-computed tomography study.

AIM: To compare root resorption (RR) after rapid maxillary expansion (RME) and slow maxillary expansion (SME) through micro-computed tomography (micro-CT). SUBJECTS AND METHODS: Twenty-six subjects who required maxillary expansion and bilateral upper first premolar extraction were randomly assigned to RME (n = 13, mean age: 13.25 ± 0.88 years) or SME (n = 13, mean age: 13.53±1.28 years) group. A hyrax-type acrylic bonded expansion appliance was used. The Hyrax screw was activated » turn twice a day for 20 days in the RME group and » turn every second day for 80 days in the SME group. One randomly selected upper first premolar was extracted in each patient after active expansion. The appliance was left in situ for a 24-week retention period then the contralateral upper first premolar was extracted. Extracted teeth were scanned with micro-CT and the volume of the resorption craters was analysed with a specialized software. Transversal skeletal and dental widths were measured on posteroanterior radiographs taken before and after expansion and retention periods. RESULTS: The resorption craters were concentrated mostly on the buccal surface and middle level in all samples. The total RR in the RME group was less post-expansion (P ≤ 0.05) and more post-retention (P > 0.05) than the SME group. During retention, there was a significant decrease in the total RR in the SME group (P > 0.05) and an increase in the RME group. Both RME and SME groups displayed a similar increase in skeletal transverse dimensions, but inter-molar width increased significantly more in the SME group during the whole experimental period. CONCLUSION: RME does not have an advantage over SME in terms of skeletal expansion and the amount of RR when a retention period of six months is followed.

Pre-hospital stroke screening and notification of patients with reperfusion-eligible acute ischaemic stroke using modified Face Arm Speech Time test.

OBJECTIVES: To investigate the effects of pre-hospital stroke screening and notification on reperfusion therapy for patients with acute ischaemic stroke. METHODS: Pre-hospital stroke screening criteria were established based on a modified version of the Face Arm Speech Time (FAST) test. Screening was performed during ambulance transport by emergency medical service (EMS) personnel who completed a 2-hour training session on stroke screening. Temporal trends affecting acute ischaemic stroke investigation and intervention were compared before and after implementation of the pre-hospital screening. RESULTS: From July 2018 to October 2019, 298 patients with suspected stroke were screened by EMS personnel during ambulance transport prior to hospital arrival. Of these 298 patients, 213 fulfilled the screening criteria, 166 were diagnosed with acute stroke, and 32 received reperfusion therapy. The onset-to-door time was shortened by more than 1.5 hours (100.6 min vs 197.6 min, P<0.001). The door-to-computed tomography time (25.6 min vs 32.0 min, P=0.021), door-to-needle time (49.2 min vs 70.1 min, P=0.003), and door-to-groin puncture time for intra-arterial mechanical thrombectomy (126.7 min vs 168.6 min, P=0.04) were significantly shortened after implementation of the pre-hospital screening and notification, compared with historical control data of patients admitted from January 2018 to June 2018, before implementation of the screening system. CONCLUSION: Implementation of pre-hospital stroke screening using criteria based on a modified version of the FAST test, together with pre-arrival notification, significantly shortened the door-to-reperfusion therapy time for patients with ischaemic stroke. Pre-hospital stroke screening during ambulance transport by EMS personnel who complete a 2-hour focused training session is effective for identifying reperfusion-eligible patients with stroke.

The effects of different sampling techniques on peripheral post mortem tryptase levels: a recommended sampling method.

Different sampling techniques can impact on post mortem tryptase levels. A previous study demonstrated significantly lower femoral post mortem total tryptase levels in samples collected via transcutaneous aspiration compared with directly sampling during internal examination. However, an outlier with high tryptase level was noted in one transcutaneous aspiration sample. This 6-month prospective study compared total post mortem tryptase levels between 21 paired aspirated venous and arterial femoral blood samples, and 19 paired aspirated and cutdown femoral venous blood samples in non-anaphylactic deaths only. No statistical differences were demonstrated between the different sampling methods. However, four outlier cases with higher tryptase levels in aspirated arterial and femoral cutdown samples compared with aspirated venous femoral samples were noted. The reasons for the outliers may be due to the bloods collected from these two methods being contaminated by central arterial and venous blood with high tryptase levels respectively. None of the aspirated venous femoral post mortem tryptase levels were above recognized post mortem tryptase cutoff to diagnose anaphylaxis. This study recommends aspirating blood samples from a clamped femoral/external iliac vein for post mortem tryptase analysis should be defined as the gold standard. Further study using the recommended sampling method on post mortem tryptase levels in non-anaphylactic and anaphylactic cases is warranted.

The 17D-204 Vaccine Strain-Induced Protection against Virulent Yellow Fever Virus Is Mediated by Humoral Immunity and CD4+ but not CD8+ T Cells.

A gold standard of antiviral vaccination has been the safe and effective live-attenuated 17D-based yellow fever virus (YFV) vaccines. Among more than 500 million vaccinees, only a handful of cases have been reported in which vaccinees developed a virulent wild type YFV infection. This efficacy is presumed to be the result of both neutralizing antibodies and a robust T cell response. However, the particular immune components required for protection against YFV have never been evaluated. An understanding of the immune mechanisms that underlie 17D-based vaccine efficacy is critical to the development of next-generation vaccines against flaviviruses and other pathogens. Here we have addressed this question for the first time using a murine model of disease. Similar to humans, vaccination elicited long-term protection against challenge, characterized by high neutralizing antibody titers and a robust T cell response that formed long-lived memory. Both CD4+ and CD8+ T cells were polyfunctional and cytolytic. Adoptive transfer of immune sera or CD4+ T cells provided partial protection against YFV, but complete protection was achieved by transfer of both immune sera and CD4+ T cells. Thus, robust CD4+ T cell activity may be a critical contributor to protective immunity elicited by highly effective live attenuated vaccines.

Family behaviours that have an impact on the self-management activities of adults living with Type 2 diabetes: a systematic review and meta-synthesis.

AIMS: To identify family behaviours that adults with Type 2 diabetes' perceive as having an impact on their diabetes self-management. BACKGROUND: Research suggests that adults with Type 2 diabetes perceive that family members have an important impact on their self-management; however, it is unclear which family behaviours are perceived to influence self-management practices. METHODS: This meta-synthesis identified and synthesized qualitative studies from the databases EMBASE, Medline and CINAHL published between the year 2000 and October 2016. Studies were eligible if they provided direct quotations from adults with Type 2 diabetes, describing the influence of families on their self-management. This meta-synthesis adheres to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. RESULTS: Of the 2606 studies screened, 40 were included. This meta-synthesis identified that adults with Type 2 diabetes perceive family behaviours to be either: 1) facilitators of diabetes self-management; 2) barriers to diabetes self-management; or 3) equivocal behaviours with the potential to both support and/or impede diabetes self-management. Seven sub-themes were identified within these themes, including: four facilitator sub-themes ('positive care partnerships'; 'family watchfulness'; 'families as extrinsic motivator' and 'independence from family'); two barrier sub-themes ('obstructive behaviours' and 'limited capacity for family support'); and one equivocal behaviours subtheme ('regular reminders and/or nagging'). CONCLUSION: While most family behaviours are unambiguously perceived by adults with Type 2 diabetes to act as facilitators of or barriers to self-management, some behaviours were perceived as being neither clear facilitators nor barriers; these were termed 'equivocal behaviours'. If the concept of 'equivocal behaviours' is confirmed, it may be possible to encourage the adult living with Type 2 diabetes to reframe these behaviours so that they are perceived as enabling their diabetes self-management.

A pragmatic comparative study of palliative care clinician's reports of the degree of shadowing visible on plain abdominal radiographs.

The assessment of constipation symptoms is based on history and physical examination. However, the experience is highly subjective perhaps explaining why palliative medicine doctors continue to use plain abdominal radiographs as part of routine assessment of constipation. Previous studies have demonstrated poor agreement between clinicians with this work in palliative care, limited further by disparity of clinicians' experience and training. The aim of this work was to explore whether there was less variation in the assessments of faecal shadowing made by more experienced clinicians compared to their less experienced colleagues. This pragmatic study was conducted across six palliative care services in Sydney (NSW, Australia). Doctors of varying clinical experience were asked to independently report their opinions of the amount of shadowing seen on 10 plain abdominal radiographs all taken from cancer patients who self-identified themselves as constipated. There were 46 doctors of varying clinical experience who participated including qualified specialists, doctors in specialist training and lastly, doctors in their second- and third post-graduate years. Poor agreement was seen between the faecal shadowing scores allocated by doctors of similar experience and training (Fleiss's kappa (FK): RMO 0.05; registrar 0.06; specialist 0.11). Further, when the levels of agreement between groups were considered, no statistically significant differences were observed. Although the doctors did not agree on the appearance of the film, the majority felt they were able to extrapolate patients' experiences from the radiograph's appearance. As it remains challenging in palliative care to objectively assess and diagnose constipation by history and imaging, uniform and objective assessment and diagnostic criteria are required. It is likely that any agreed criteria will include a combination of imaging and history. The results suggest the use of radiographs alone to diagnose and assess constipation in palliative care represents low value care.

Validation of Fear of Falling and Balance Confidence Assessment Scales in Persons With Dystonia.

BACKGROUND AND PURPOSE: Falls are problematic for people living with neurological disorders and a fear of falling can impact on actual falls. Fear of falling is commonly assessed using the Falls Self-Efficacy Scale International (FES-I) or the Activities-specific Balance Confidence (ABC) Scale. These scales can predict risk of falling. We aimed to validate the FES-I and the ABC in persons with dystonia. METHODS: We conducted an online survey of people with dystonia, collecting information on demographics, 6-month falls history, dystonia disability, and the FES-I and ABC scales. Scales were validated for structural validity and internal consistency. We also examined goodness-of-fit, convergent validity, and predictive validity, and determined cutoff scores for predicting falls risk. RESULTS: Survey responses (n = 122) showed that both FES-I and ABC scales have high internal validity and convergent validity with the Functional Disability Questionnaire in persons with dystonia. Each scale examines a single factor, fear of falling (FES-I) and balance confidence (ABC). At least one fall was reported by 39% of participants; the cutoff value for falls risk was found to be 29.5 and 71.3 for the FES-I and the ABC respectively. DISCUSSION AND CONCLUSIONS: The FES-I and the ABC scales are valid scales to examine fear of falling and balance confidence in persons with dystonia. Fear of falling is high and balance confidence is low and both are worse in those with dystonia who have previously fallen.Video Abstract available for more insights from the authors (see Video, Supplemental Digital Content 1, http://links.lww.com/JNPT/A182).

Clinical trials of medicinal cannabis for appetite-related symptoms from advanced cancer: a survey of preferences, attitudes and beliefs among patients willing to consider participation.

BACKGROUND: Australian clinical trials are planned to evaluate medicinal cannabis in a range of clinical contexts. AIMS: To explore the preferences, attitudes and beliefs of patients eligible and willing to consider participation in a clinical trial of medicinal cannabis for poor appetite and appetite-related symptoms from advanced cancer. METHODS: A cross-sectional anonymous survey was administered from July to December 2015 online and in eight adult outpatient palliative care and/or cancer services. Respondents were eligible if they were ≥18 years, had advanced cancer and poor appetite/taste problems/weight loss and might consider participating in a medicinal cannabis trial. Survey items focused on medicinal rather than recreational cannabis use and did not specify botanical or pharmaceutical products. Items asked about previous medicinal cannabis use and preferences for delivery route and invited comments and concerns. RESULTS: There were 204 survey respondents, of whom 26 (13%) reported prior medicinal cannabis use. Tablets/capsules were the preferred delivery mode (n = 144, 71%), followed by mouth spray (n = 84, 42%) and vaporiser (n = 83, 41%). Explanations for preferences (n = 134) most commonly cited convenience (n = 66; 49%). A total of 82% (n = 168) of respondents indicated that they had no trial-related concerns, but a small number volunteered concerns about adverse effects (n = 14) or wanted more information/advice (n = 8). Six respondents volunteered a belief that cannabis might cure cancer, while two wanted assurance of efficacy before participating in a trial. CONCLUSION: Justification of modes other than tablets/capsules and variable understanding about cannabis and trials will need addressing in trial-related information to optimise recruitment and ensure that consent is properly informed.

Amine oxidase activity of ß-amyloid precursor protein modulates systemic and local catecholamine levels.

The catecholamines dopamine (DA), norepinephrine (NE) and epinephrine (E) are neurotransmitters and hormones that mediate stress responses in tissues and plasma. The expression of ß-amyloid precursor protein (APP) is responsive to stress and is high in tissues rich in catecholamines. We recently reported that APP is a ferroxidase, subsuming, in neurons and other cells, the iron-export activity that ceruloplasmin mediates in glia. Here we report that, like ceruloplasmin, APP also oxidizes synthetic amines and catecholamines catalytically (K(m) NE=0.27 mM), through a site encompassing its ferroxidase motif and selectively inhibited by zinc. Accordingly, APP knockout mice have significantly higher levels of DA, NE and E in brain, plasma and select tissues. Consistent with this, these animals have increased resting heart rate and systolic blood pressure as well as suppressed prolactin and lymphocyte levels. These findings support a role for APP in extracellular catecholaminergic clearance.