Appendectomy has long been the mainstay of intervention for acute appendicitis, aiming at preventing perforation, peritonitis, abscess formation and recurrence. With better understanding of the ...disease process, non-operative management (NOM) with antibiotics alone has been proved a feasible treatment for uncomplicated appendicitis. This article aimed at systematically reviewing the available literatures and discussing the question whether NOM should replace appendectomy as the standard first-line treatment for uncomplicated appendicitis.
A search of the Embase, Pubmed and Cochrane Library was performed using the keywords 'acute appendicitis' and 'antibiotic therapy'. Meta-analysis with inverse variance model for continuous variable and Mantel Haenzel Model for dichotomous variable was performed to evaluate the one year treatment efficacy, morbidities rate, sick leave duration and length of hospital stay associated with emergency appendectomy and NOM.
Six randomized control trials were identified out of 1943 publications. NOM had a significant lower treatment efficacy rate at one year, 0.10 (95% CI 0.03-0.36,
< 0.01), when compared to appendectomy. The morbidities rate was comparable between the two interventions. The length of hospital stay was longer, with a mean difference of 1.08 days (95% CI 0.09-2.07,
= 0.03), and the sick leave duration was shorter, a mean difference of 3.37 days (95% CI -5.90 to -0.85 days,
< 0.01) for NOM.
The paradigm remains unchanged, that appendectomy is the gold standard of treatment for uncomplicated appendicitis, given its higher efficacy rate when compared to NOM.
Objective
With increasing prevalence of childhood obesity worldwide, the incidence of pediatric‐onset type 2 diabetes (T2D) is also increasing in many countries. We aim to analyze the time trend and ...incidence of T2D in children in Hong Kong from 2008 to 2017, and to characterize clinical characteristics at diagnosis.
Methods
Data were retrieved from the Hong Kong Childhood Diabetes Registry. All children with T2D diagnosed at the age of less than 18 years from January 1, 2008 to December 31, 2017 and managed in the public health care system were included in this study.
Results
In the incident years of 2008–2017 period, 391 children were diagnosed with T2D. The crude incidence rate was 3.42 per 100,000 persons/year 95% confidence interval (CI) 3.08–3.76, which was much higher than that in last registry of 1.27 per 100,000 persons/year in 1997–2007 (P < 0.001).Most children (76%) were asymptomatic and were diagnosed by routine screening. At presentation, a significant proportion presented with co‐morbidities including fatty liver (37.9%), dyslipidaemia (35.3%), hypertension (22.5%), and microalbuminuria (12.8%).
Conclusions
The incidence of T2D in children has increased significantly in Hong Kong. Most of them were asymptomatic and picked up on routine health screening. Yet, comorbidities were commonly identified at diagnosis.
Abstract Background The adverse effects of a long duration of untreated psychosis (DUP) have been explored in numerous short-term studies. These studies support the development of early interventions ...that reduce treatment delay and promote recovery. However, the enduring impact of DUP is largely unknown, partly due to the paucity of prospective long-term studies. Although the DUP–outcome relationship is commonly assumed to be linear, the threshold effect has not been adequately examined. Objective To explore the relationship between DUP and long-term symptomatic remission. Methods This was a prospective study of a cohort of 153 first-episode psychosis patients in Hong Kong at the 13-year follow-up. The patients were categorized into short (≤ 30 days), medium (31–180 days) and long (> 180 days) DUP groups. Results The long-term outcome was ascertained in 73% of the patients. Nearly half of the patients (47%) fulfilled the criteria for symptomatic remission. The short DUP group experienced a significantly higher remission rate over the course of the illness. The odds of long-term symptomatic remission was significantly reduced in the medium DUP (by 89%) and long DUP (by 85%) groups compared with the short DUP group. Further analysis showed that DUP had a specific impact on negative symptom remission. Conclusion The findings support the threshold theory that DUP longer than 30 days adversely impacts the long-term outcome. The present study is one of the few studies that confirmed the enduring impact of DUP on long-term outcomes based on well-defined criteria and adequate statistical adjustment.
Obesity and type 2 diabetes mellitus (T2DM) are growing health concerns. Since 2005, Student Health Service (SHS) and Hong Kong Paediatric Society formulated a protocol on urine glucose screening ...(UGS) for early diagnosis of T2DM in students with obesity in Hong Kong. This study reviews students with T2DM captured by this screening program and compare the data with the Hong Kong Children Diabetes Registry (HKCDR) database, to see if the UGS program facilitates early diagnosis of T2DM.
Students between the ages of 10-18 years old with age- and sex-specific body mass index (BMI) >97th percentile who attended SHS between the school years from 2005/06 to 2017/18 were recruited for UGS. Those tested positive for random urine glucose underwent diagnostic testing for T2DM according to ADA guidelines. Demographic data and investigatory results from UGS and HKCDR within the same time period were compared.
A total of 216,526 students completed UGS in the said period; 415 (0.19 %) students were tested positive for urine glucose of which 121 students were diagnosed with T2DM. UGS picked up 23 % of the newly diagnosed T2DM cases. When compared to the HKCDR database, students diagnosed via UGS were significantly younger, less obese, and had fewer diabetic related complications. The negative predictive value of UGS is high and can effectively rule out T2DM.
Urine glucose screening is an inexpensive and simple test that allows for early diagnosis of T2DM among obese school students. Other methods including POCT HbA
can be explored to improve program effectiveness.
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Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and ...Alzheimer’s disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N–H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies.
Abstract Semantic categorization abnormalities have been observed in schizophrenia, but studies have rarely focused on the longitudinal trajectory. In this study, we consider semantic performance and ...the relationship with symptomatic changes during recovery from a first-episode of schizophrenia over a period of 3 years. Thirty-seven first-episode patients with schizophrenia were compared to thirty-seven matched controls in a categorization task. Patients were assessed at first episode, after clinical stabilization, and annually for the subsequent 3 years. In the task, participants indicated whether a word belonged to a given category. Each category contained words of varying degrees of semantic relatedness: typical, atypical, borderline, related-but-outside, and unrelated. Reaction times and proportion of ‘yes’ responses were analyzed. At first assessment, semantic categorization abnormalities were observed in first-episode patients. Patients assigned more semantically-dissimilar words to the categories than controls. As patients stabilized from acute states, their semantic categorization performance improved and then remained stable throughout the entire follow up period of 3 years. Interestingly, semantic performance deficits, particularly a diminished typicality effect, correlated with negative symptoms in the initial episode, but not at stabilization when symptoms subsided. No significant associations between positive and negative symptoms, or pre-defined categorization measures were identified. The data demonstrated semantic memory abnormalities in first-episode schizophrenia. However, an improvement of semantic categorization performance was observed in stabilized schizophrenia patients. Overall, the data are suggestive of a state effect in semantic abnormalities rather than a trait effect. The correlation between degree of impairment and symptoms may explain previous inconsistent findings.
Close monitoring after diagnosis of patients with stage I-III non-small cell lung cancer (NSCLC) may result in fitter patients with lower disease burden at the time of metastatic recurrence or ...progression compared to patients diagnosed initially as stage IV (de novo). We compared the presentation, treatments, and outcomes of patients with KRASG12C-mutated NSCLC with de novo versus recurrent stage IV disease. Of 109 patients, 94% had a smoking history. When compared to patients with KRASG12C-mutated NSCLC who developed stage IV disease at recurrence (n = 38), de novo stage IV patients (n = 71) had worse ECOG performance status (p = 0.007), greater numbers of extra-thoracic metastatic sites (p = 0.001), and were less likely to receive 2nd/3rd line systemic therapy (p = 0.05, p = 0.002) or targeted therapy (p = 0.001). De novo metastatic patients had shorter overall survival than metastatic patients at recurrence (9.1 versus 24.2 months; adjusted-hazard-ratio=1.94 (95% CI: 1.14-3.28; p = 0.01)). There is a critical need for well-tolerated targeted therapies in the first-line setting for metastatic patients with de novo, high-burden, stage IV KRASG12C-mutated NSCLCs.
Abstract Objective To investigate the risk of gonadal germ cell neoplasms (GCN) in children with 45,X/46,XY gonadal dysgenesis and its relation to the clinical presentations. Methods We conducted a ...retrospective study reviewing the clinical and gonadal features of all consecutive children with 45,X/46,XY gonadal dysgenesis who received gonadal management in a tertiary center from 1985 to 2015. Study subjects were divided into Group I(significant genitalia anomaly), Group II(female phenotype) and Group III(male phenotype). Results 21 children were studied (Group I = 8; Group II = 11; Group III = 2). All 19 children of Group I and II eventually underwent bilateral gonadectomy. One patient of Group III underwent gonadal biopsy which showed increase in fibrous tissue in the testes without any GCN. 3/8(37.5%) and 6/11(54.5%) of patients in Group I and II respectively had either gonadoblastoma (GB) or carcinoma-in-situ (CIS) or both affecting one or both gonads. Among Group I patients, the 4 dysgenetic testes affected by CIS in 3 patients were intraabdominal ( n = 1), inguinal ( n = 1) and scrotal ( n = 2) in positions. Among Group II patients, 6/20 streak gonads had GB and 2/2 dysgenetic testes had GB or CIS. Conclusions 45,X/46,XY children with significant genitalia anomaly or female phenotype are both at high risk of gonadal GCN.
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern such as Omicron hampered efforts in controlling the ongoing coronavirus disease 2019 pandemic due to ...their ability to escape neutralizing antibodies induced by vaccination or prior infection, highlighting the need to develop broad-spectrum vaccines and therapeutics. Most human monoclonal antibodies (mAbs) reported to date have not demonstrated true pan-sarbecovirus neutralizing breadth especially against animal sarbecoviruses. Here, we report the isolation and characterization of highly potent mAbs targeting the receptor binding domain (RBD) of huACE2-dependent sarbecovirus from a SARS-CoV survivor vaccinated with BNT162b2. Among the six mAbs identified, one (E7) showed better huACE2-dependent sarbecovirus neutralizing potency and breadth than any other mAbs reported to date. Mutagenesis and cryo-electron microscopy studies indicate that these mAbs have a unique RBD contact footprint and that E7 binds to a quaternary structure-dependent epitope.