Evaluation of deformed image-based dose calculations for adaptive radiotherapy of nasopharyngeal carcinoma

The ultimate goal of adaptive radiotherapy (ART) is to deliver truly customized radiation treatments. Currently, the quality of cone-beam computed tomography (CBCT) images is still inferior to that of conventional CT images in contour delineations and dose calculations for replanning purposes. This retrospective study aims to evaluate the dosimetric accuracy of using deformed conventional CT images for dose calculations, in the hope of inferring the feasibility of ART using planning CT (PCT) images that deformed to up-to-date CBCT images for patients with nasopharyngeal carcinoma (NPC). Thirty consecutive patients with NPC who had undergone 1 replan in their radiotherapy treatments were selected. The pretreatment PCT images were deformed to match the mid-treatment PCT images by deformable image registration. The same volumetric modulated arc therapy plan was then calculated on the deformed PCT images. The resulting dose distributions and dose volume histograms of the tumors and organs at risk (OARs) were compared with the original plan. Five dose levels, D98%, D95%, D50%, D5%, and D2%, were recorded for 9 NPC targets. Four dose levels, Dmax, D10%, D50%, and Dmean, were recorded for 15 OARs. The greatest percentage difference in observed dose for D98%, D95%, D50%, D5%, and D2% of the targets were 1.71%, 1.55%, 0.64%, 0.97%, and 1.13%, respectively. The greatest percentage difference in observed dose for Dmax, D10%, D50%, and Dmean of the OARs were -26.51% (left optic nerve), -17.06% (left optic nerve), 56.70% (spinal cord), and 18.97% (spinal cord), respectively. In addition, 29 of 45 (64%) dosimetric end points of the targets showed statistically significant dose differences (p < 0.05) between the original plan and the plan calculated on deformed images. Forty-nine of 60 (82%) dosimetric end points of the OARs also showed statistically significant dose differences (p < 0.05). Dose calculations using deformed PCT images could result in significant dose uncertainties in target volumes and OARs. Larger dose deviations were found in OARs in comparison with target volumes. The spinal cord and optic nerve showed the greatest percentage dose differences and the clinical significance has yet to be determined. Deformable registration error was believed to be the problem causing the dose deviations. Owing to unknown clinical significanceof dose deviation results obtained from this study, a conventional CT scan is still required for replanning in patients with NPC who are experiencing significant anatomical changes during the course of radiation treatment. [Abstract copyright: Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Phospho-aspirin (MDC-22) inhibits breast cancer in preclinical animal models: an effect mediated by EGFR inhibition, p53 acetylation and oxidative stress

BACKGROUND: The anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we synthesized phospho-aspirin (PA-2; MDC-22), a novel derivative of aspirin, and evaluated its chemotherapeutic and chemopreventive efficacy in preclinical models of triple negative breast cancer (TNBC). METHODS: Efficacy of PA-2 was evaluated in human breast cancer cells in vitro, and in orthotopic and subcutaneous TNBC xenografts in nude mice. Mechanistic studies were also carried out to elucidate the mechanism of action of PA-2. RESULTS: PA-2 inhibited the growth of TNBC cells in vitro more potently than aspirin. Treatment of established subcutaneous TNBC xenografts (MDA-MB-231 and BT-20) with PA-2 induced a strong growth inhibitory effect, resulting in tumor stasis (79% and 90% inhibition, respectively). PA-2, but not aspirin, significantly prevented the development of orthotopic MDA-MB-231 xenografts (62% inhibition). Mechanistically, PA-2: 1) inhibited the activation of epidermal growth factor receptor (EGFR) and suppressed its downstream signaling cascades, including PI3K/AKT/mTOR and STAT3; 2) induced acetylation of p53 at multiple lysine residues and enhanced its DNA binding activity, leading to cell cycle arrest; and 3) induced oxidative stress by suppressing the thioredoxin system, consequently inhibiting the activation of the redox sensitive transcription factor NF-κB. These molecular alterations were observed in vitro and in vivo, demonstrating their relevance to the anticancer effect of PA-2. CONCLUSIONS: Our findings demonstrate that PA-2 possesses potent chemotherapeutic efficacy against TNBC, and is also effective in its chemoprevention, warranting further evaluation as an anticancer agent

Renal and Splenic Micro-Infarctions Following Bronchial Artery Embolization with Tris-Acryl Microspheres

A bronchial artery embolization (BAE) is an important therapeutic method used to control acute and chronic hemoptysis. We report a case of multiple micro-infarcts involving both the kidneys and spleen, following a BAE with 500-700 µm crossed-linked tris-acryl microspheres (Embospheres) in a patient with bronchial artery pulmonary vein shunts. The superior penetration characteristics of the microspheres may have resulted in the greater tendency to cross the bronchial artery pulmonary vein shunts, which subsequently caused the systemic infarcts in our patient. We propose the use of larger sized microspheres (700-900 µm), which may aid in avoiding this complication

Hong Kong Renal Registry Report 2012

SummaryThis report examined the characteristics and trends of dialysis and renal transplant patients among the resident population of Hong Kong who were managed by hospitals or dialysis centers of the Hospital Authority, and accounted for approximately 95% of all patients receiving renal replacement therapies (RRTs) in the territory. Patients receiving RRTs solely in the private sector were not included in this report. Data trends from 1996 to 2011 are presented. In 2011, 1115 new patients were accepted into RRT programs, and the incident rate was 157 patients per million populations (pmp). An increasing trend was noted. The incident rate was 95.1 pmp at the commencement of the annual report in 1996. The point prevalence on December 31, 2012 was 8197 with a prevalence rate of 1152.5 pmp. Overall, there were 3573 patients (43.6%) on peritoneal dialysis (PD) and 1246 patients (15.2%) on hemodialysis (HD), and 3378 patients (41.2%) were living with a functioning renal transplant. The PD/HD ratio was 74.2:25.8. The “PD First” policy was continued. The overall mortality rate among RRT patients was 9.95 patients per 100 patient-years exposed. There was a decreasing trend in mortality among PD patients. Infection and cardiovascular complications were the most common causes of death. Renal transplant was the modality with the best survival rates. The 5 years cumulative patient survival rate for patients on transplant treatment was 89.6%, whereas the corresponding patient survival rates for PD and HD patients were 50.7% and 55.7%, respectively. More than 70% of RRT patients with reports on rehabilitation were active and had normal daily activities

Comparisons of the risk of myopericarditis between COVID-19 patients and individuals receiving COVID-19 vaccines: a population-based study.

Both COVID-19 infection and COVID-19 vaccines have been associated with the development of myopericarditis. The objective of this study is to (1) analyse the rates of myopericarditis after COVID-19 infection and COVID-19 vaccination in Hong Kong, (2) compared to the background rates, and (3) compare the rates of myopericarditis after COVID-19 vaccination to those reported in other countries. This was a population-based cohort study from Hong Kong, China. Patients with positive RT-PCR test for COVID-19 between 1st January 2020 and 30th June 2021 or individuals who received COVID-19 vaccination until 31st August were included. The main exposures were COVID-19 positivity or COVID-19 vaccination. The primary outcome was myopericarditis. This study included 11,441 COVID-19 patients from Hong Kong, four of whom suffered from myopericarditis (rate per million: 326; 95% confidence interval [CI] 127-838). The rate was higher than the pre-COVID-19 background rate in 2019 (rate per million: 5.5, 95% CI 4.1-7.4) with a rate ratio of 55.0 (95% CI 21.4-141). Compared to the background rate, the rate of myopericarditis among vaccinated subjects in Hong Kong was similar (rate per million: 5.5; 95% CI 4.1-7.4) with a rate ratio of 0.93 (95% CI 0.69-1.26). The rates of myocarditis after vaccination in Hong Kong were comparable to those vaccinated in the United States, Israel, and the United Kingdom. COVID-19 infection was associated with significantly higher rate of myopericarditis compared to the vaccine-associated myopericarditis. [Abstract copyright: © 2022. The Author(s).

Chronic adiponectin deficiency leads to Alzheimer’s disease-like cognitive impairments and pathologies through AMPK inactivation and cerebral insulin resistance in aged mice

(a) Immunoblotting analysis of IRβ in the hippocampus and frontal cortex of 18-month old wildtype and APN-KO mice. (b) Densitometric analysis of the ratio of IRβ. Mean ± S.E.M.; ***p < 0.001, n.s. statistically not significant; Scale bar: 100 μm. (JPG 30 kb

Sulfonylurea is associated with higher risks of ventricular arrhythmia or sudden cardiac death compared with metformin: A population-based cohort study

Background Commonly prescribed diabetic medications such as metformin and sulfonylurea may be associated with different arrhythmogenic risks. This study compared the risk of ventricular arrhythmia or sudden cardiac death between metformin and sulfonylurea users in patients with type 2 diabetes. Methods and Results Patients aged ≥40 years who were diagnosed with type 2 diabetes or prescribed antidiabetic agents in Hong Kong between January 1, 2009, and December 31, 2009, were included and followed up until December 31, 2019. Patients prescribed with both metformin and sulfonylurea or had prior myocardial infarction were excluded. The study outcome was a composite of ventricular arrhythmia or sudden cardiac death. Metformin users and sulfonylurea users were matched at a 1:1 ratio by propensity score matching. The matched cohort consisted of 16 596 metformin users (47.70% men; age, 68±11 years; mean follow‐up, 4.92±2.55 years) and 16 596 sulfonylurea users (49.80% men; age, 70±11 years; mean follow‐up, 4.93±2.55 years). Sulfonylurea was associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin hazard ratio (HR, 1.90 [95% CI, 1.73–2.08]). Such difference was consistently observed in subgroup analyses stratifying for insulin usage or known coronary heart disease. Conclusions Sulfonylurea use is associated with higher risk of ventricular arrhythmia or sudden cardiac death than metformin in patients with type 2 diabetes

Comparing hybrid and regular COVID-19 vaccine-induced immunity against the Omicron epidemic

Evidence on the effectiveness of COVID-19 vaccines among people who recovered from a previous SARS-CoV-2 infection is warranted to inform vaccination recommendations. Using the territory-wide public healthcare and vaccination records of over 2.5 million individuals in Hong Kong, we examined the potentially differential risk of SARS-CoV-2 infection, hospitalization, and mortality between those receiving two homologous doses of BNT162b2 or CoronaVac versus those with a previous infection receiving only one dose amid the Omicron epidemic. Results show a single dose after a SARS-CoV-2 infection is associated with a lower risk of infection (BNT162b2: adjusted incidence rate ratio [IRR] = 0.475, 95% CI: 0.410–0.550; CoronaVac: adjusted IRR = 0.397, 95% CI: 0.309–0.511) and no significant difference was detected in the risk of COVID-19-related hospitalization or mortality compared with a two-dose vaccination regimen. Findings support clinical recommendations that those with a previous infection could receive a single dose to gain at least similar protection as those who received two doses without a previous infection

Promotion of knowledge and awareness of parents in HK about infant oral health care

Aim: To promote the knowledge and awareness of infant oral health (OH) care among Hong Kong parents with children aged 0 to 2 years through an interactive workshop and to evaluate its effectiveness. Methods: Parents were recruited from government-registered childcare centers and private playgroups. Interactive workshops consisted of a 30-minute PowerPoint presentation and 20 minutes of small-group activities, which included infant oral hygiene instruction with custom-made infant dentition models, diet analysis and question-and-answer session. Self-completed questionnaires used to evaluate the knowledge and attitude of parents were distributed before and after the workshops. Scores on general OH knowledge (range=0-18), infant OH knowledge (0-10) and parent’s attitude (0-4) were computed. Scores of at least 70% were considered proficient. Results: Among the 111 participants (aged 26 to 54 years, 64% mothers), 96% had a child aged 0 to 30 months. 30% had their children’s mouth cleaned at least twice a day. Only one participant had brought his/her child to see a dentist. Weaker aspects in parents’ OH knowledge and common misconceptions were identified in the pre-survey. Only 35% identified frequent meals as an increased caries risk; only 59% and 79% identified starchy food and formula milk as cariogenic food respectively. 58% did not know water fluoridation can prevent caries, while 33% of parents pointed out calcium supplement can prevent caries. Before the workshop, 41% had proficient general OH knowledge (mean=11.9) and 16% had proficient infant OH knowledge (mean=4.8). Over half of parents showed positive attitude (mean=3.4). Significant improvements in general OH knowledge (mean=15.6, p<0.001), infant OH knowledge (mean=8.8, p<0.001) and attitude (mean=3.9, p<0.001) were observed. Parents reflected the workshops were useful (94%) and they learned new practices to improve their infants’ OH (95%). Conclusion: Several deficiencies in oral health knowledge and behaviour are identified. The interactive workshops can effectively promote the knowledge and awareness of infant oral health care among parents with children aged 0 to 2 years. Large-scale infant oral health survey is needed. Interactive workshops with longer follow-up periods are recommended. More guidelines can be provided to parents and general dentists for prevention of caries.published_or_final_versio

Handgrip strength assessment at baseline in addition to bone parameters could potentially predict the risk of curve progression in adolescent idiopathic scoliosis

IntroductionAdolescent idiopathic scoliosis (AIS) is characterized by deranged bone and muscle qualities, which are important prognostic factors for curve progression. This retrospective case–control study aims to investigate whether the baseline muscle parameters, in addition to the bone parameters, could predict curve progression in AIS.MethodsThe study included a cohort of 126 female patients diagnosed with AIS who were between the ages of 12 and 14 years old at their initial clinical visit. These patients were longitudinally followed up every 6 months (average 4.08 years) until they reached skeletal maturity. The records of these patients were thoroughly reviewed as part of the study. The participants were categorized into two sub-groups: the progressive AIS group (increase in Cobb angle of ≥6°) and the stable AIS group (increase in Cobb angle &lt;6°). Clinical and radiological assessments were conducted on each group.ResultsCobb angle increase of ≥6° was observed in 44 AIS patients (34.9%) prior to skeletal maturity. A progressive AIS was associated with decreased skeletal maturity and weight, lower trunk lean mass (5.7%, p = 0.027) and arm lean mass (8.9%, p &lt; 0.050), weaker dominant handgrip strength (8.8%, p = 0.027), deranged cortical compartment [lower volumetric bone mineral density (vBMD) by 6.5%, p = 0.002], and lower bone mechanical properties [stiffness and estimated failure load lowered by 13.2% (p = 0.005) and 12.5% (p = 0.004)]. The best cut-off threshold of maximum dominant handgrip strength is 19.75 kg for distinguishing progressive AIS from stable AIS (75% sensitivity and 52.4% specificity, p = 0.011).DiscussionPatients with progressive AIS had poorer muscle and bone parameters than patients with stable AIS. The implementation of a cut-off threshold in the baseline dominant handgrip strength could potentially be used as an additional predictor, in addition to bone parameters, for identifying individuals with AIS who are at higher risk of experiencing curve progression