Comparison of safety and efficacy between Nirmatrelvir-ritonavir and molnupiravir in the treatment of COVID-19 infection in patients with advanced kidney disease: a retrospective observational study.

Background: Nirmatrelvir-ritonavir is used in patients with coronavirus disease 2019 (COVID-19) with normal or mild renal impairment (eGFR ≥30 ml/min per 1.73 m2). There is limited data regarding its use in advanced kidney disease (eGFR <30 ml/min per 1.73 m2). We performed a retrospective territory-wide observational study evaluating the safety and efficacy of nirmatrelvir-ritonavir when compared with molnupiravir in the treatment of patients with COVID-19 with advanced kidney disease. Methods: We adopted target trial emulation using data from a territory-wide electronic health record database on eligible patients aged ≥18 years with advanced kidney disease (history of eGFR <30 ml/min per 1.73 m2) who were infected with COVID-19 and were prescribed with either molnupiravir or nirmatrelvir-ritonavir within five days of infection during the period from 16 March 2022 to 31 December 2022. A sequence trial approach and 1:4 propensity score matching was applied based on the baseline covariates including age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index (CCI), hospitalisation, eGFR, renal replacement therapy, comorbidities (cancer, respiratory disease, myocardial infarction, ischaemic stroke, diabetes, hypertension), and drug use (renin-angiotensin-system agents, beta blockers, calcium channel blockers, diuretics, nitrates, lipid lowering agents, insulins, oral antidiabetic drugs, antiplatelets, immuno-suppressants, corticosteroids, proton pump inhibitors, histamine H2 receptor antagonists, monoclonal antibody infusion) within past 90 days. Individuals were followed up from the index date until the earliest outcome occurrence, death, 90 days from index date or the end of data availability. Stratified Cox proportional hazards regression adjusted with baseline covariates was used to compare the risk of outcomes between nirmatrelvir-ritonavir recipients and molnupiravir recipients which include (i) all-cause mortality, (ii) intensive care unit (ICU) admission, (iii) ventilatory support, (iv) hospitalisation, (v) hepatic impairment, (vi) ischaemic stroke, and (vii) myocardial infarction. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (≤5; >5), and number of COVID-19 vaccine doses received (0-1; ≥2 doses). Findings: A total of 4886 patients were included (nirmatrelvir-ritonavir: 1462; molnupiravir: 3424). There were 347 events of all-cause mortality (nirmatrelvir-ritonavir: 74, 5.06%; molnupiravir: 273, 7.97%), 10 events of ICU admission (nirmatrelvir-ritonavir: 4, 0.27%; molnupiravir: 6, 0.18%), 48 events of ventilatory support (nirmatrelvir-ritonavir: 13, 0.89%; molnupiravir: 35, 1.02%), 836 events of hospitalisation (nirmatrelvir-ritonavir: 218, 23.98%; molnupiravir: 618, 28.14%), 1 event of hepatic impairment (nirmatrelvir-ritonavir: 0, 0%; molnupiravir: 1, 0.03%), 8 events of ischaemic stroke (nirmatrelvir-ritonavir: 3, 0.22%; molnupiravir: 5, 0.16%) and 9 events of myocardial infarction (nirmatrelvir-ritonavir: 2, 0.15%; molnupiravir: 7, 0.22%). Nirmatrelvir-ritonavir users had lower rates of all-cause mortality (absolute risk reduction (ARR) at 90 days 2.91%, 95% CI: 1.47-4.36%) and hospitalisation (ARR at 90 days 4.16%, 95% CI: 0.81-7.51%) as compared with molnupiravir users. Similar rates of ICU admission (ARR at 90 days -0.09%, 95% CI: -0.4 to 0.2%), ventilatory support (ARR at 90 days 0.13%, 95% CI: -0.45 to 0.72%), hepatic impairment (ARR at 90 days 0.03%, 95% CI: -0.03 to 0.09%), ischaemic stroke (ARR at 90 days -0.06%, 95% CI: -0.35 to 0.22%), and myocardial infarction (ARR at 90 days 0.07%, 95% CI: -0.19 to 0.33%) were found between nirmatrelvir-ritonavir and molnupiravir users. Consistent results were observed in relative risk adjusted with baseline characteristics. Nirmatrelvir-ritonavir was associated with significantly reduced risk of all-cause mortality (HR: 0.624, 95% CI: 0.455-0.857) and hospitalisation (HR: 0.782, 95% CI: 0.64-0.954). Interpretation: Patients with COVID-19 with advanced kidney disease receiving nirmatrelvir-ritonavir had a lower rate of all-cause mortality and hospital admission when compared with molnupiravir. Other adverse clinical outcomes were similar in both treatment groups. Funding: Health and Medical Research Fund (COVID1903010), Health Bureau, The Government of the Hong Kong Special Administrative Region, China.

Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial.

BACKGROUND: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤3 cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. INTERVENTION: Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. RESULTS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1-yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS: In patients with NMIBC of ≤3 cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR (funded by GRF/ECS, RGC, reference no.: 24116518; ClinicalTrials.gov number, NCT02993211). PATIENT SUMMARY: Conventionally, non-muscle-invasive bladder cancer is treated by resecting the bladder tumour in a piecemeal manner. In this study, we found that en bloc resection, that is, removal of the bladder tumour in one piece, could reduce the 1-yr recurrence rate of non-muscle-invasive bladder cancer.

Dissecting the effects of METTL3 on alternative splicing in prostate cancer.

Although the role of METTL3 has been extensively studied in many cancers, its role in isoform switching in prostate cancer (PCa) has been poorly explored. To investigate its role, we applied standard RNA-sequencing and long-read direct RNA-sequencing from Oxford Nanopore to examine how METTL3 affects alternative splicing (AS) in two PCa cell lines. By dissecting genome-wide METTL3-regulated AS events, we noted that two PCa cell lines (representing two different PCa subtypes, androgen-sensitive or resistant) behave differently in exon skipping and intron retention events following METTL3 depletion, suggesting AS heterogeneity in PCa. Moreover, we revealed that METTL3-regulated AS is dependent on N6-methyladenosine (m6A) and distinct splicing factors. Analysis of the AS landscape also revealed cell type specific AS signatures for some genes (e.g., MKNK2) involved in key functions in PCa tumorigenesis. Finally, we also validated the clinical relevance of MKNK2 AS events in PCa patients and pointed to the possible regulatory mechanism related to m6A in the exon14a/b region and SRSF1. Overall, we characterize the role of METTL3 in regulating PCa-associated AS programs, expand the role of METTL3 in tumorigenesis, and suggest that MKNK2 AS events may serve as a new potential prognostic biomarker.

The influence of changes in the Chinese COVID-19 prevention and control policies on mental health of medical staff: A network analysis.

BACKGROUND: Shortly after the first outbreak of COVID-19 in Wuhan, the disease spread rapidly around the world. Previous findings reported an increase in mental health problems among Chinese medical staff, but there was a lack of research following changes in COVID-19 prevention and control policies. METHODS: Medical staff were recruited separately in China from 15 to 16 December 2022 (N = 765, wave 1) and from 5 to 8 January 2023 (N = 690, wave 2). All participants completed the assessments of Generalized Anxiety Disorder-7, the Patient Health Questionnaire-9 and the Euthymia Scale. Network analysis was used to explore the relationships between symptoms both within and across depression, anxiety and euthymia. RESULTS: Medical staff showed worse anxiety, depression and euthymia at wave 2 than at wave 1. Depression, motor, restlessness and uncontrollable worrying showed high centrality (i.e., strength, expected influence, closeness) at wave 1, but higher at peak. Meanwhile, motor symptoms and restlessness showed the strongest connection between different mental disorders at both wave 1 and wave 2. The network structure was stable over time after the relaxation of the infection policy. LIMITATIONS: Our participants were not a random sample and the assessments were based on self-reports. CONCLUSIONS: This study indicated the changes in central and bridging symptoms in medical staff at different stages after lifting of restrictions and the withdrawal of testing requirements, which provided management suggestions for the Chinese government and hospitals, as well as clinical guidance for psychological interventions.

Language impairments in children with developmental language disorder and children with high-functioning autism plus language impairment: Evidence from Chinese negative sentences.

There is controversy as to whether children with developmental language disorder (DLD) and those with high-functioning autism plus language impairment (HFA-LI) share similar language profiles. This study investigated the similarities and differences in the production of Chinese negative sentences by children with DLD and children with HFA-LI to provide evidence relevant to this controversy. The results reflect a general resemblance between the two groups in their lower-than-TDA (typically developing age-matched) performance. Both groups encountered difficulties in using negative markers, which suggests that they might be impaired in feature agreement. Slight differences were detected between the two groups. Specifically, children with DLD experienced difficulties with the agreement on the feature [+telic] and that on the feature [+dynamic], while children with HFA-LI had difficulties with the agreement on the feature [+dynamic] and that on the feature [-dynamic]. This study supports the idea of a common symptomatology for the two disorders. More importantly, it suggests that these two disorders, DLD and HFA-LI, are not altogether the same in terms of language impairment. This paper concludes that general labels should not be simply attached to any children with language disorders. Instead, atypical language is very worthy of further analysis in the categorization of language disorders.

A Wide-bandwidth Nanocomposite-Sensor Integrated Smart Mask for Tracking Multi-phase Respiratory Activities for COVID-19 Endemic

A global sentiment in early 2022 is that the COVID-19 virus could become endemic just like common cold flu viruses soon. The most optimistic view is that, with minimal precautions, such as vaccination, boosters and optional masking, life for most people will proceed as normal soon. However, as warned by A. Katzourakis of Oxford University recently [1], we must set aside lazy optimism, and must be realistic about the likely levels of death, disability and sickness that will be brought on by a COVID-19 endemic. Moreover, the world must also consider that continual circulation of the virus could give rise to new variants such as the new BA.2 variant (a subvariant of Omicron) continues to spread across the US and parts of Europe. Data from the CDC is already showing that BA.2 has been tripling in prevalence every two weeks [2]. Hence, globally, we must use available and proven weapons to continue to fight the COVID-19 viruses, i.e., effective vaccines, antiviral medications, diagnostic tests and stop an airborne virus transmission through social distancing, and mask wearing. For this work, we have demonstrated a smart mask with an optimally-coupled ultra-thin flexible soundwave sensors for tracking, classifying, and recognizing different respiratory activities, including breathing, speaking, and two-/tri-phase coughing; the masks functionality can also be augmented in the future to monitor other human physiological signals. Although researchers have integrated sensors into masks to detect respiratory activities in the past, they only based on measuring temperature and air flow during coughing, i.e., counting only the number of coughs. However, coughing is a process consisting of several phases, including an explosion of the air with glottal opening producing some noise-like waveform, a decrease of airflow to decrease sound amplitude, and a voiced stage which is the interruption of the air flow due to the closure of glottal and periodical vibration of partly glottis, which is not always present. Therefore, sensors used for cough detection should not be only sensitive to subtle air pressure but also the high-frequency vibrations, i.e., a pressure sensor that needs to be responsive to a wide input amplitude and bandwidth range, in order to detect air flows between hundreds of hertz from breath, and acoustic signals from voice that could reach [~] 8000 Hz. Respiratory activities data from thirty-one (31) human subjects were collected. Machine learning methods such as Support Vector Machines and Convolutional Neural Networks were used to classify the collected sensor data from the smart mask, which show an overall macro-recall of about 93.88% for the three respiratory sounds among all 31 subjects. For individual subjects, the 31 human subjects have the average macro-recall of 95.23% (ranging from 90% to 100%) for these 3 respiratory activities. Our work bridges the technological gap between ultra-lightweight but high-frequency response sensor material fabrication, signal transduction and conditioning, and applying machining learning algorithms to demonstrate a reliable wearable device for potential applications in continual healthy monitoring of subjects with cough symptoms during the eventual COVID-19 endemic. The monitoring and analysis of cough sound should be highly beneficial for human health management. These health monitoring data could then be shared with doctors via cloud storage and transmission technique to help disease diagnosis more effectively. Also, communication barriers caused by wearing masks can be alleviated by combining with the speech recognition techniques. In general, this research helps to advance the wearable device technology for tracking respiratory activities, similar to an Apple Watch or a Fitbit smartwatch in tracking physical and physiological activities.

Significance of the 'line sign' in the diagnosis of congenital imperforate anus on prenatal ultrasound.

BACKGROUND: The prenatal diagnosis of foetal imperforate anus is difficult. Most previous studies have been case reports. To provide useful information for diagnosing foetal imperforate anus, a retrospective review of diagnostic approaches was conducted. Ultrasonography was performed in 19 cases of foetal imperforate anus from 2016 to 2019 at our prenatal diagnostic centre. The prenatal sonographic features and outcomes of each case were collected and evaluated. RESULT: The anal sphincter of a normal foetus shows the 'target sign' on cross-sectional observation. Of the 19 cases of imperforate anus, 16 cases were diagnosed by the ultrasound image feature called the 'line sign'. 1 case with tail degeneration was low type imperforate anus with the irregular 'target sign' not a real 'target sign'. There was two false-negative case, in which the 'target sign' was found, but irregular. CONCLUSION: In this study, we find that the anus of a foetus with imperforate anus presents a 'line sign' on sonographic observation. The absence of the 'target sign' and then the presence of the 'line sign' can assist in the diagnosis of imperforate anus. The 'line sign' can be used as a secondary assessment to determine the type of the malformation following non visualization of the 'target sign'. The higher the position of the imperforate anus is, the more obvious the 'line sign'. It is worth noting that the finding of the short 'line sign' and irregularr 'target sign' can not ignore the low type imperforate anus.

How Can We Support Online Learning for Elementary Students? Perceptions and Experiences of Award-Winning K-6 Teachers.

K-12 online learning can be advantageous in a variety of circumstances, including inclement weather days and emergency remote teaching. With the lessons learned from the COVID-19 pandemic, many K-12 districts may consider ways to incorporate online learning into their regular school plans after they resume face-to-face instruction. However, the most challenges to online learning seemed to take place at the elementary level. This brings up an important question: What should elementary online teaching and learning look like? We examined six award-winning K-6 teachers' perspectives on and experiences with online instruction and practices for elementary students. The teachers suggested that online instruction to support elementary students' learning should be (a) organized, (b) engaging, and (c) interactive. Teachers also suggested that developmentally appropriate use of technology and parental involvement may foster elementary students' online learning experiences.

Nasal prevention of SARS-CoV-2 infection by intranasal influenza-based boost vaccination

BackgroundVaccines in emergency use are efficacious against COVID-19, yet vaccine-induced prevention against nasal SARS-CoV-2 infection remains suboptimal. MethodsSince mucosal immunity is critical for nasal prevention, we investigated an intramuscular PD1-based receptor-binding domain (RBD) DNA vaccine (PD1-RBD-DNA) and intranasal live attenuated influenza-based vaccines (LAIV-CA4-RBD and LAIV-HK68-RBD) against SARS-CoV-2. FindingsSubstantially higher systemic and mucosal immune responses, including bronchoalveolar lavage IgA/IgG and lung polyfunctional memory CD8 T cells, were induced by the heterologous PD1-RBD-DNA/LAIV-HK68-RBD as compared with other regimens. When vaccinated animals were challenged at the memory phase, prevention of robust SARS-CoV-2 infection in nasal turbinate was achieved primarily by the heterologous regimen besides consistent protection in lungs. The regimen-induced antibodies cross-neutralized variants of concerns. Furthermore, LAIV-CA4-RBD could boost the BioNTech vaccine for improved mucosal immunity. InterpretationOur results demonstrated that intranasal influenza-based boost vaccination is required for inducing mucosal and systemic immunity for effective SARS-CoV-2 prevention in both upper and lower respiratory systems. FundingThis study was supported by the Research Grants Council Collaborative Research Fund (C7156-20G, C1134-20G and C5110-20G), General Research Fund (17107019) and Health and Medical Research Fund (19181052 and 19181012) in Hong Kong; Outbreak Response to Novel Coronavirus (COVID-19) by the Coalition for Epidemic Preparedness Innovations; Shenzhen Science and Technology Program (JSGG20200225151410198); the Health@InnoHK, Innovation and Technology Commission of Hong Kong; and National Program on Key Research Project of China (2020YFC0860600, 2020YFA0707500 and 2020YFA0707504); and donations from the Friends of Hope Education Fund. Z.C.s team was also partly supported by the Theme-Based Research Scheme (T11-706/18-N).

SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury

Robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.

Comparison of laparoscopic versus open gastrectomy for gastric cancer.

BACKGROUND: This study aimed to compare the short-term and long-term outcomes of laparoscopic gastrectomy (LG) and open gastrectomy (OG) for gastric cancer in a tertiary referral center in Hong Kong. METHODS: Two hundred and ninety-four consecutive patients with gastric cancer who underwent radical gastrectomy with curative intent between January 2008 and December 2015 were analyzed. Data was prospectively collected and reviewed. Propensity score matching was applied at a ratio of 1:1 to compare the OG and LG groups. RESULTS: After propensity score matching, operation duration (294.7 vs 231.8min, P < 0.01) was significantly longer while estimated blood loss (191.6 vs 351.0 ml, P = 0.01) was significantly less in LG group compared with OG. There were no significant differences in postoperative complications and mortality between LG and OG groups (postoperative complication rate, 35.2% vs 40.7%, P = 0.69; 90-day mortality rate, 1.9% vs 3.7%, P = 1.00). Three-year OS and 3-yr DFS of patients who underwent LG was not inferior to that of patients who had OG (P = 0.34; P = 0.51). However, there were significantly more peritoneal recurrences among the OG group than LG group (P < 0.01). CONCLUSIONS: LG has comparable outcomes for gastric cancer, even in advanced tumors. We could appropriately increase the proportion of laparoscopic gastrectomy for gastric cancer.

The application of prenatal ultrasound in the diagnosis of congenital duodenal obstruction.

BACKGROUND: The purpose of this research is to summarize the prenatal ultrasound characteristics of congenital duodenal obstruction (CDO), especially in the diagnosis of duodenal diaphragm and annular pancreas. At present, few researchers have summarized the specific ultrasound features of duodenal diaphragm and annular pancreas. METHODS: In this study, a retrospective analysis of 40 patients diagnosed with CDO between January 2016 and December 2019 was carried out. Data on the diagnosis, ultrasound images and outcomes of the patients were gathered, and the features of the patients were analyzed. RESULTS: The results showed that there were 17 patients (42.5%) of congenital duodenal diaphragm, all with a 'rat tail' sign on the ultrasound images. Moreover, there were 4 patients (10.0%) of CDO caused by annular pancreas, all with a 'pliers' sign on the ultrasound images. We summarized the imaging features of the 'rat tail' sign and the 'pliers' sign. CONCLUSION: The main conclusion of this study was that the 'rat tail' sign could be used as an indirect ultrasound feature to diagnose duodenal diaphragm. The 'pliers' sign could be used as a direct ultrasound feature in the diagnosis of annular pancreas in CDO.

Prenatal diagnosis of fetal intraabdominal extralobar pulmonary sequestration: a 12-year 3-center experience in China.

To provide useful information for diagnosing and predicting fetal intraabdominal extralobar pulmonary sequestration (IEPS), a retrospective review of diagnostic approaches was conducted. Ultrasonography was performed serially in 21 fetuses with IEPS from 2005 to 2017. Prenatal sonographic features, treatment, and outcomes of each case were evaluated and collected. These cases of IEPS were also compared to 43 cases previously reported by other researchers from 1986 to 2017. Of the 21 sonographic features, 14 (67%) were hyperechoic, 21 (100%) were well circumscribed, and 17 (81%) depicted a mass that shifted with fetal breaths/hiccups non-synchronized with adjacent organs (sliding sign). Feeding arteries were detected prenatally in 18 patients (86%). The lesion volume was 10.17 ± 4.66 cm3, the congenital cystic adenomatoid malformation volume ratio and cardiothoracic ratio were in normal range. The gestational age at diagnosis, location and echotexture of the lesion, and rate of surgical treatment were similar to previous studies, but with a significantly higher rate of detected feeding arteries (P < 0.01), and associated anomalies (P < 0.01). All infants who underwent surgery after birth had satisfactory outcomes. The sliding sign and feeding artery are essential features of IEPS in prenatal diagnosis.

Transurethral resection of prostate for acute urinary retention is linked to shorter survival in younger men / 亚洲男科学杂志(英文版)

It is largely unknown whether lower urinary tract symptoms (LUTS) or acute retention of urine (AROU) is linked to shorter life expectancy in men. We conducted a multicenter, retrospective database analysis of patients undergoing transurethral resection of prostate (TURP) to study their relationships. Multivariate Cox regression analysis and Kaplan-Meier analysis with stratification to age and indication of TURP were performed. We further performed an age- and sex-matched survival analysis with the general population using data from the Census and Statistics Department of the Hong Kong Special Administrative Region (Hong Kong, China). From January 2002 to December 2012, 3496 patients undergoing TURP were included in our study, with 1764 patients in the LUTS group and 1732 patients in the AROU group. Old age, ischemic heart disease, cerebrovascular accident, and AROU were risk factors of mortality. Patients aged <70 years (adjusted hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.11-2.09, P = 0.010) and 70-80 years (adjusted HR: 1.39, 95% CI: 1.15-1.70, P = 0.001) in the AROU group had worse survival than those in the LUTS group, but such difference was not demonstrated in patients aged >80 years. Compared to the general population, younger patients in the LUTS group appeared to have better survival (<70 years, P = 0.091; 70-80 years, P = 0.011), but younger patients in the AROU group had worse survival (<70 years, P = 0.021; 70-80 years, P = 0.003). For patients aged >80 years, survival was similar with the general population in both the LUTS and AROU groups. In conclusion, AROU at young age was associated with mortality, while early detection and management of LUTS may improve survival.

FA01.01: MINIMALLY INVASIVE APPROACH RESULTS IN BETTER OUTCOME COMPARED TO OPEN ESOPHAGECTOMY-A PROPENSITY SCORE MATCHED ANALYSIS.

BACKGROUND: Esophagectomy remains the mainstay treatment for esophageal cancer. Minimally invasive techniques have gained popularity in recent years. Whether minimally invasive methods result in equivalent or superior outcome to open esophagectomy or not is still controversial. The aim of the current study is to compare outcomes of minimally invasive and open esophagectomy from a single institution, using propensity score matching to lessen biases. METHODS: From 1994-2016, 724 patients with squamous cell cancer of the esophagus who underwent esophagectomy were studied. Data were retrieved from a prospectively collected database. Patients were divided into two groups: 453 had open esophagectomy (open group), and 271 had VATS esophagectomy with gastric mobilization either via laparotomy or laparoscopically (MIE group). A propensity score was generated for each patient based on age, gender, tumor level, use of neoadjuvant therapy, American Society of Anaesthesiologists (ASA) score, pathologic stage of disease, site of anastomosis, and residual tumour (R) categories and the two matched groups were compared in clinico-pathological features, morbidity and mortality rates, and long-term survival. All statistical calculations were performed with SPSS version 24 (SPSS, Chicago, IL). RESULTS: A total of 158 patients in MIE and 187 in open group are matched for comparison (1:3 matching). MIE resulted in less blood loss (220 vs 400ml, P < 0.001) but longer operative time (461 vs 305 mins, P < 0.001). Wound infection (3.7% vs 10.7%, P = 0.01) and respiratory complications (29% vs 55.1%, P < 0.001) were also less in MIE group. Except for a higher rate of conduit ischemia (6.3% vs 1.6%, P = 0.02), MIE had comparable surgical outcomes with open technique in rates of anastomotic leakage (5.7% vs 5.3%, P = 0.89), recurrent laryngeal nerve palsy (20.1% vs 18.7%, P = 0.10), reoperation (10.8% vs 8.6%, P = 0.49), and length of postoperative hospital stay (13 vs 14 days, P = 0.50). Lymph node harvest was significantly higher with MIE (35 vs 21, P < 0.001), a longer median survival was also evident compared to the open group (42.3 vs 24.7 months, P = 0.03). CONCLUSION: Although requiring longer operative time, MIE led to less wound and respiratory complications without jeopardizing surgical and oncological outcome. The more comprehensive lymphadenectomy could potentially improve prognosis. DISCLOSURE: All authors have declared no conflicts of interest.

The Role of Vitamin D in the Pathogenesis of Adolescent Idiopathic Scoliosis

Several theories have been proposed to explain the etiology of adolescent idiopathic scoliosis (AIS) until present. However, limited data are available regarding the impact of vitamin D insufficiency or deficiency on scoliosis. Previous studies have shown that vitamin D deficiency and insufficiency are prevalent in adolescents, including AIS patients. A series of studies conducted in Hong Kong have shown that as many as 30% of these patients have osteopenia. The 25-hydroxyvitamin D3 level has been found to positively correlate with bone mineral density (BMD) in healthy adolescents and negatively with Cobb angle in AIS patients; therefore, vitamin D deficiency is believed to play a role in AIS pathogenesis. This study attempts to review the relevant literature on AIS etiology to examine the association of vitamin D and various current theories. Our review suggested that vitamin D deficiency is associated with several current etiological theories of AIS. We postulate that vitamin D deficiency and/or insufficiency affects AIS development by its effect on the regulation of fibrosis, postural control, and BMD. Subclinical deficiency of vitamin K2, a fat-soluble vitamin, is also prevalent in adolescents; therefore, it is possible that the high prevalence of vitamin D deficiency is related to decreased fat intake. Further studies are required to elucidate the possible role of vitamin D in the pathogenesis and clinical management of AIS.

Combining levodopa and virtual reality-based therapy for rehabilitation of the upper limb after acute stroke: pilot study Part II

<p><b>INTRODUCTION</b>This study aimed to evaluate the safety and efficacy of a combination of levodopa and virtual reality (VR)-based therapy for the enhancement of upper limb recovery following acute stroke.</p><p><b>METHODS</b>This was a pilot single-blinded case series of acute stroke patients with upper extremity hemiparesis. Patients were randomised to standard care with concomitant administration of either levodopa alone (control group) or combination therapy consisting of VR-based motivational visuomotor feedback training with levodopa neuromodulation (VR group). Main clinical outcome measures were the Fugl-Meyer Upper Extremity (FM-UE) assessment and Action Research Arm Test (ARAT). Kinematic measurements of affected upper limb movement were evaluated as a secondary measure of improvement.</p><p><b>RESULTS</b>Of 42 patients screened, four patients were enrolled in each of the two groups. Two patients dropped out from the control group during the trial. Patients receiving combination therapy had clinically significant improvements in FM-UE assessment scores of 16.5 points compared to a 3.0-point improvement among control patients. Similarly, ARAT scores of VR group patients improved by 15.3 points compared to a 10.0-point improvement in the control group. Corresponding improvements were noted in kinematic measures, including hand-path ratio, demonstrating that the quality of upper limb movement improved in the VR group.</p><p><b>CONCLUSION</b>Our results suggest that VR-based therapy and pharmacotherapy may be combined for acute stroke rehabilitation. Bedside acquisition of kinematic measurements allows accurate assessment of the quality of limb movement, offering a sensitive clinical tool for quantifying motor recovery during the rehabilitation process after acute stroke.</p>

[Association of colorectal adenoma and metabolic syndrome and relevant parameters].

OBJECTIVE: To evaluate the association of colorectal adenoma with metabolic syndrome (MS) and relevant parameters. METHODS: Clinical data of 289 subjects who underwent screening colonoscopy in the University of Hong Kong-Shenzhen Hospital from January 2014 to June 2015 were retrospectively analyzed, including 130 normal subjects (normal group) and 159 cases with colorectal adenoma confirmed by pathology(adenoma group). Levels of MS-associated parameters were compared between the two groups, and the association of metabolic diseases with colorectal adenoma was examined. RESULTS: The gender, smoking and drinking habit, regular physical activity, family history of colorectal cancer, and consumption history of long-term non-steroidal anti-inflammatory drugs were not significantly different between two groups (all P>0.05). As compared to normal group, adenoma group had higher body mass index (BMI) [(23.5±3.2) kg/m(2) vs. (22.7±2.8) kg/m(2), t=1.97, P=0.050], larger abdominal circumference [(83.4±10.3) cm vs. (79.6±13.8) cm, t=2.46, P=0.015], higher serum high-density lipoprotein level [(1.3±0.3) mmol/L vs. (1.2±0.3) mmol/L, t=2.03, P=0.044], and higher serum cholesterol [(5.4±1.0) mmol/L vs. (5.0±1.1) mmol/L, t=2.39, P=0.018]. No significant difference was demonstrated in comparing hip circumference and waist-hip ratio, as well as serum fasting glucose and triglyceride(all P>0.05). Higher incidence of colorectal adenoma was found in subjects with MS [69.8%(37/53) vs. 1.7%(122/236), P=0.017], overweight or obesity [65.1% (56/86) vs. 50.7%(103/203), P=0.025], hypertension [67.3%(37/55) vs. 52.1%(122/234), P=0.046] and hypercholesterolemia [66.7%(64/96) vs. 49.2%(95/193), P=0.005]. CONCLUSIONS: Metabolic syndrome increased the risk of developing colorectal adenoma. The mechanism may be related to higher serum cholesterol and high density lipoprotein, which may lead to the elevated catabolism of serum cholesterol. Screening colonoscopy should be performed for patients diagnosed as metabolic syndrome, especially for those with central obesity and hypercholesterolemia, thus early diagnosis and treatment of colorectal adenoma may be available.

Hypnotic effects of a novel anti-insomnia formula on Drosophila insomnia model / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the biological effects of the six-herb mixture Anti-Insomia Formula (AIF) extract using caffeine-induced insomnia Drosophila model and short-sleep mutants.</p><p><b>METHODS</b>Caffeineinduced insomnia wild-type Drosophila and short-sleep mutant flies minisleep (mns) and Hyperkinetic(Y) (Hk(Y)) were used to assess the hypnotic effects of the AIF in vivo. The night time activity, the amount of night time sleep and the number of sleep bouts were determined using Drosophila activity monitoring system. Sleep was defined as any period of uninterrupted behavioral immobility (0 count per minute) lasting > 5 min. Night time sleep was calculated by summing up the sleep time in the dark period. Number of sleep bouts was calculated by counting the number of sleep episodes in the dark period.</p><p><b>RESULTS</b>AIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness (P<0.01) in wild-type Canton-S flies as indicated by the reduction of the sleep bouts, night time activities and increase of the amount of night time sleep. AIF also significantly reduced sleeping time of short-sleep Hk(Y) mutant flies (P<0.01). However, AIF did not produce similar effect in mns mutants.</p><p><b>CONCLUSION</b>AIF might be able to rescue the abnormal condition caused by mutated modulatory subunit of the tetrameric potassium channel, but not rescuing the abnormal nerve firing caused by Shaker gene mutation. This study provides the scientific evidence to support the use of AIF in Chinese medicine for promoting sleep quality in insomnia.</p>

The use of virtual reality-based therapy to augment poststroke upper limb recovery

Stroke remains one of the major causes of disability worldwide. This case report illustrates the complementary use of biomechanical and kinematic in-game markers, in addition to standard clinical outcomes, to comprehensively assess and track a patient's disabilities. A 65-year-old patient was admitted for right-sided weakness and clinically diagnosed with acute ischaemic stroke. She participated in a short trial of standard stroke occupational therapy and physiotherapy with additional daily virtual reality (VR)-based therapy. Outcomes were tracked using kinematic data and conventional clinical assessments. Her Functional Independence Measure score improved from 87 to 113 and Fugl-Meyer motor score improved from 56 to 62, denoting clinically significant improvement. Corresponding kinematic analysis revealed improved hand path ratios and a decrease in velocity peaks. Further research is being undertaken to elucidate the optimal type, timing, setting and duration of VR-based therapy, as well as the use of neuropharmacological adjuncts.