Probiotic supplementation demonstrates therapeutic potential in treating gut dysbiosis and improving neurocognitive function in age-related dementia.

PURPOSE: Probiotics, as live microorganisms that improve intestinal microbial balance, have been implicated in the modulation of neurodegenerative diseases via the microbiome-gut-brain axis by improving gut dysbiosis. This review examines the association between probiotics and neurocognitive function in age-related dementia. METHODS: We searched MEDLINE, Embase, Scopus, Web of Science and Cochrane library for in vivo studies using equivalent combinations of "probiotics" and "dementia" as per PRISMA. From the 52 in vivo studies identified, 5 human and 22 animal studies with comparable quantitative outcomes on neurocognitive/behavioural function were meta-analysed by forest plots, subgroup analysis and meta-regression. The analysis of biomarkers, risk of bias and publication bias were also performed. RESULTS: In elderly humans, probiotics correlates with a non-significant difference of neurocognitive function in Mini-Mental State Examination, but with significant improvement only in those diagnosed with Alzheimer's disease. In animals, probiotics significantly improved neurocognitive function as measured by Morris Water Maze, Y-Maze, and Passive Avoidance. Further analysis by subgrouping and meta-regression found that the probiotics-neurodegeneration association is age dependent in humans but is neither dose dependent nor duration dependent in animals or humans. Analysis of biomarkers suggested that the neurocognitive effect of probiotics is associated with an altered gut microbiome profile, downregulated proteinopathic, inflammatory and autophagic pathways, and upregulated anti-oxidative, neurotrophic, and cholinergic pathways. CONCLUSION: Overall, we report promising results in animal studies but limited evidence of probiotics leading to neurocognitive improvement in humans. More research into probiotics should be conducted, especially on live biotherapeutic products for targeted treatment of gut dysbiosis and age-related dementia.

The epidemiology of inflammatory bowel disease: East meets west.

The incidence of inflammatory bowel diseases (IBD) in East has risen over the past decade to become a global disease. The increasing number of studies on the incidence and course of IBD in East has enabled us to explore East versus West differences in the epidemiology of IBD which could enhance our understanding of the heterogeneity of the disease and eventually assist in the discovery of novel therapeutic targets and design of preventive strategies. Comparison of population-based data in East and West reveals that the incidence of IBD has risen rapidly in East while plateauing in West. Furthermore, the clinical presentation and course of IBD differs between East and West with more patients in East presenting with complicated disease. Considering the scarcity of population-based data from East and the lack of studies with long durations of follow-up, it remains to be clarified whether these differences reflect true differences in disease presentation. The effects of genetic and environmental risk factors contributing to IBD also differ between Eastern and Western populations. Considering the differential effects of genetic and environmental risk factors in East and West, future studies should seek to discover novel genetic and environmental risk factors which might specifically apply to eastern populations. In this narrative review, we compare the epidemiology of IBD between eastern and western countries by summarizing evidence from population-based cohort studies in the last ten years. Furthermore, we look at differences in genetic susceptibility and environmental triggers of IBD between East and West.

Territory-wide population-based study of chronic hepatitis C infection and implications for hepatitis elimination in Hong Kong.

BACKGROUND: To study the epidemiology of chronic hepatitis C virus infection in Hong Kong and to estimate the service gap for achieving the WHO hepatitis elimination targets of attaining a diagnosis rate of 90%, treatment rate of 80% and 65% reduction in mortality rate by 2030. METHODS: From January 2005 to March 2017, patients who were tested positive for anti-HCV were retrospectively retrieved from all public hospitals in Hong Kong. The epidemiological data of 15 participating hospitals were analysed. RESULTS: A total of 11 309 anti-HCV+ patients were identified and the estimated diagnosis rate was 50.9%. Our HCV-infected patients were ageing (median age 59). The all-cause mortality rate increased from 26.2 to 54.8 per 1000 person-years over the last decade. Our estimated treatment rate was 12.4%. Among the treated patients, 93.6% had received pegylated interferon/ribavirin (Peg-IFN/RBV) but only 10.8% had received interferon-free direct-acting antivirals (DAAs). In a cohort of 1533 patients, 39% already had advanced liver fibrosis or cirrhosis. The sustained virological response rate for Peg-IFN/RBV and DAAs were 74.8% and 97.2% respectively. However, more than 70% of patients were not subjected to interferon treatment for various reasons. Patients who achieved SVR were associated with a significantly lower risk of HCC (4.7% vs 9.6%, P = 0.005) and death (1.7% vs 23.8%, P < 0.001). CONCLUSION: Our diagnosis rate, treatment rate and mortality rate reduction were still low, particularly the Peg-IFN outcomes, making it difficult to meet the WHO hepatitis elimination targets. A more generalized use of DAAs is urgently needed to improve the situation.

Fecal Calprotectin in Assessing Endoscopic and Histological Remission in Patients with Ulcerative Colitis.

BACKGROUND: Persistent active endoscopic and histological inflammation is associated with poorer outcomes in ulcerative colitis (UC). Fecal calprotectin is a surrogate marker of endoscopic and histological remission. AIMS: To confirm the correlation between fecal calprotectin and endoscopic or histological disease activity and to define the optimal cutoff value to detect endoscopic and histological remission. METHODS: From a prospectively maintained database, we analyzed 61 UC patients who had fecal calprotectin measurement and endoscopy performed within 1 month. Endoscopic activity was graded using the Mayo endoscopic subscore (MES). Histological remission was defined as normal histology or quiescent histological activity. RESULTS: Eighteen patients (29.5%) and five patients (8.1%) had endoscopic remission defined as MES ≤ 1 or MES = 0, respectively. We observed a significantly lower median level of fecal calprotectin in patients with endoscopic remission than those with endoscopic activity for both definition of endoscopic remission, i.e., MES ≤ 1 (158 vs 490 µg/g, p = 0.0005) or MES = 0 (94 vs 414 µg/g, p = 0.013). Seven patients (11.5%) were in histological remission. They had a lower median level of fecal calprotectin than those with active histological inflammation (107 vs 416 µg/g, p = 0.016). Using a ROC curve, fecal calprotectin < 250 µg/g predicted endoscopic remission (MES ≤ 1) with a sensitivity of 67% and specificity of 77%, while fecal calprotectin < 200 µg/g predicted histological remission with a sensitivity of 71% and specificity of 76%. CONCLUSION: Fecal calprotectin level correlated with both endoscopic activity and histological activity and is a reliable biomarker in assessing mucosal healing in UC.

Chinese medicine for residual symptoms of COVID-19 recovered patients (long COVID)-A double-blind, randomized, and placebo-controlled clinical trial protocol.

Introduction: Coronavirus disease 2019 (COVID-19) is the current global pandemic of which residual symptoms exhibited by post-acute, rehabilitating patients include fatigue, dyspnoea, and insomnia. Chinese medicine (CM) has been widely used in China to treat different stages of COVID-19. While there are a significant number of clinical studies suggesting its efficacy and safety in its use during acute stage, there are very few randomized controlled trials focusing on the rehabilitation stage. Liujunzhi Decoction and Shashen Maidong Decoction are frequently recommended by official clinical guidelines in China to treat COVID-19 patients in rehabilitation stage. This double-blind, randomized, placebo controlled study aims to evaluate the efficacy and safety of the combination of the two formulae [named "COVID-19 Rehab Formula (CRF)"] in treating COVID-19 residual symptoms (long COVID). Methods: Eligible subjects will be randomly divided into treatment group and control group in 1:1 ratio. Treatment group will receive CRF along with certain pre-defined CM according to symptoms for 8 weeks, while control group will receive equivalent packs of placebo for 8 weeks. Data in terms of Fatigue Severity Score (FSS), self-reported COVID-19 long term symptom assessment, the modified British Medical Research Council (mMRC) Dyspnoea Scale, EuroQol Five-Dimension Five-Level (EQ-5D-5L) Questionnaire, pulmonary function test and adverse events will be collected and analyzed by SPSS 24. Blood test on liver and renal functions will also be conducted as safety measures. Conclusion: This study will evaluate the efficacy and safety of CRF in the treatment COVID-19 residual symptoms in a scientifically rigorous design. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT04924881].

Fecal Calprotectin Is Highly Effective to Detect Endoscopic Ulcerations in Crohn's Disease Regardless of Disease Location.

BACKGROUND: As the reliability of fecal calprotectin (Fcal) remains debatable to detect endoscopic ulcerations in patients with pure ileal Crohn's disease (CD), we aimed to compare its performances with those observed in patients with colonic or ileocolonic location. METHODS: Using a prospectively maintained database, we analyzed 123 CD patients with Fcal measurement and ileocolonoscopy performed within 1 month with no therapeutic intervention during this interval. Receiver operating characterstic curves (ROC) were used to determine the best Fcal threshold to detect endoscopic ulcerations, taking into account the clinical relevance and usual recommended indices. Sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) were presented with 95% confidence intervals. RESULTS: The mean Fcal level was significantly higher in patients with endoscopic ulcerations in the L1 group (P = 0.025) and the L2-L3 group (P < 0.001). Using ROC curves, Fcal >200 µg/g and Fcal >250 µg/g were the best thresholds to detect endoscopic ulcerations in the L1 group (sensitivity = 75.0, 95% CI, 47.6-92.7; specificity = 87.5, 95% CI, 67.6-97.3; PPV = 80.0, 95% CI, 51.9-95.7; and NPV = 84.0; 95% CI, 63.9-95.5) and in the L2-L3 group (sensitivity = 84.1 95% CI, 69.9-93.4; specificity = 74.4, 95% CI, 57.9-87.0; PPV = 78.7, 95% CI, 64.3-89.3, and NPV = 80.6, 95% CI, 64.0-91.8), respectively. We compared the AUC between L1 and L2-L3 groups, and no difference was shown (0.89 vs 0.84, respectively, P = 0.46). We also compared 2-by-2 sensitivity, specificity, PPV, NPV, and accuracy and we did not observe any significant difference. CONCLUSION: Fecal calprotectin is highly effective to detect endoscopic ulcerations regardless of CD location but requires a lower cutoff value in patients with pure ileal involvement.

High prevalence of extended-spectrum beta-lactamase organisms and the COVID-19 pandemic impact on donor recruitment for fecal microbiota transplantation in Hong Kong.

BACKGROUND: With increasing number of clinical trials relating to fecal microbiota transplantation (FMT), it is crucial to identify and recruit long-term, healthy, and regular fecal donors. OBJECTIVE: We aimed to report the outcomes of screening and recruitment of fecal donors for FMT. METHODS: Potential donors were recruited via advertisement through internal mass emails at a university. They were required to undergo a pre-screening telephone interview, a detailed questionnaire, followed by blood and stool investigations. RESULTS: From January 2017 to December 2020, 119 potential donors were assessed with 75 failed pre-screening. Reasons for failure included: inability to come back for regular and long-term donation (n = 19), high body mass index (n = 17), underlying chronic illness or on long-term medications (n = 11), being healthcare professionals (n = 10), use of antibiotics within 3 months (n = 5) and others (n = 13). Forty-four donors completed questionnaires and 11 did not fulfill the clinical criteria. Of the remaining 33 potential donors who had stool and blood tests, 21 failed stool investigations (19 extended-spectrum beta-lactamase [ESBL] organisms, one Clostridioides difficile, one C. difficile plus Methicillin Resistant Staphylococcus aureus), one failed blood tests (high serum alkaline phosphatase level), one required long-term medication and nine withdrew consent and/or lost to follow-up. In total, only one out of 119 (0.8%) potential donors was successfully recruited as a regular donor. CONCLUSION: There was a high failure rate in donor screening for FMT. Main reasons for screening failure included high prevalence of positive ESBL organisms in stool and failed commitment to regular stool donation.

Sociolinguistic awareness and false belief in young Cantonese learners of English.

In this study, we examined whether sociolinguistic awareness and false belief were uniquely related in 3- and 4-year-old Cantonese-speaking children learning English as a second language. The English-use background of these children varied so that they possessed sociolinguistic awareness to different degrees. Results indicated that sociolinguistic awareness predicted false belief uniquely after controlling for age, nonverbal intelligence, English vocabulary, and family income for both the second language learners and the more balanced bilinguals. The group difference in false belief was adequately explained by the corresponding difference in sociolinguistic awareness over and above the other variables. Such findings provide evidence for the claim that false belief understanding is critically related to sociolinguistic awareness, which in turn is influenced by how a second language is learned.

Faecal Calprotectin Is a Very Reliable Tool to Predict and Monitor the Risk of Relapse After Therapeutic De-escalation in Patients With Inflammatory Bowel Diseases.

AIMS: To assess faecal calprotectin [Fcal] levels before and after therapeutic de-escalation, to predict clinical relapse in patients with inflammatory bowel disease [IBD]. METHODS: From a prospectively maintained database, we enrolled 160 IBD patients [112 Crohn's disease/48 ulcerative colitis] in clinical remission, with Fcal measured within 8 weeks before therapeutic de-escalation. Clinical relapse was defined using the Harvey-Bradshaw index or Simple Clinical Colitis Activity Index. RESULTS: Using a receiver operating characteristic [ROC] curve, Fcal >100 µg/g was the best threshold to predict clinical relapse after therapeutic de-escalation (area under the curve [AUC] = 0.84). In multivariate analysis, clinical remission >6 months before therapeutic de-escalation (hazard ratio [HR] = 0.57 [0.33-0.99]; p = 0.044) was associated with decreased risk of relapse, whereas current steroid medication ( = 1.67[1.00-2.79]; p <0.0001) was a risk factor. Fcal >100 µg/g was predictive of clinical relapse (HR = 3.96 [2.47-6.35]; p < 0.0001) in the whole cohort but also in patients receiving anti-tumour necrosis factor [TNF] agents [n = 85 patients; p <0.0001], anti-integrins [n = 32; p = 0.003], or no biologics [n = 43; p = 0.049], or attempting to discontinue steroids [n = 37; p = 0.001]. One patient [1/98] and seven patients [7/88, 8.0%] with baseline Fcal <100 µg/g relapsed within 3 months and 6 months after therapeutic de-escalation, respectively. A total of 74 Fcal measurements were performed in 52 patients after therapeutic de-escalation. Monitoring Fcal >200 µg/g [ROC curve with AUC = 0.96] was highly predictive of clinical relapse in multivariate analysis ([HR = 31.8 [3.5-289.4], p = 0.002). Only two relapses [2/45, 4.4%] occurred within 6 months while Fcal <200 µg/g. CONCLUSIONS: Fcal level is highly accurate to predict and monitor the risk of relapse after therapeutic de-escalation in IBD patients and could be used in daily practice.

Twenty years of biological therapy in an patient with IBD.

This interesting case is the first to our knowledge to report outcomes of a patient with Crohn's disease (CD) treated with the biological drug, infliximab, for around 20 years. The case highlights the positive effect of long-term use of infliximab in achieving and maintaining remission in a patient with CD.In this case, loss of response to infliximab was not dependent on length of exposure to the drug. It also appeared that infliximab was still efficacious after drug holidays, which can be especially important around times of pregnancy. Of interest, 'loss of response' to infliximab occurred at one particular time point. The drug was then reintroduced at a later date, which gave the patient clinical benefit. This case suggests that in some situations infliximab can be reintroduced in patients with previous 'loss of response'.Importantly, in this case, Infliximab had no major adverse effects during the 20 years follow-up.

Significant Medical and Surgical Morbidity in Perianal Crohn's Disease: Results from a Territory-Wide Study.

BACKGROUND: The presence of perianal fistulas in Crohn's disease [CD] denotes increased disease aggressiveness. We studied the epidemiology and clinical outcomes of perianal CD [PCD] using the Hong Kong territory-wide IBD Registry [HKIBDR]. METHODS: Consecutive patients with PCD were identified from the HKIBDR, and disease characteristics, treatments, and outcomes were analysed. The risks for medical and surgical therapies were assessed using Kaplan-Meier analysis. RESULTS: Among 981 patients with CD with 10530 patient-years of follow-up, 283 [28.8%] had perianal involvement, of which 120 [42.4%] were as first presentation. The mean age at diagnosis of PCD was 29.1 years, and 78.8% were male. The median follow-up duration was 106 months (interquartile range [IQR]: 65-161 months]. Perianal fistula [84.8%] and perianal abscess [52.7%] were the two commonest forms. Male, younger age at diagnosis of CD, and penetrating phenotypes were associated with development of PCD in multivariate analysis. Of 242 patients with fistulizing PCD, 70 [29.2%] required ≥5 courses of antibiotics, and 98 [40.5%] had ≥2 surgical procedures. Nine patients required defunctioning surgery and 4 required proctectomy. Eighty-four patients [34.7%] received biologics. Cumulative probabilities for use of biologics were 4.7%, 5.8%, and 8.6% at 12 months, 36 months, and 96 months, respectively, while the probabilities for surgery were 67.2%, 71.6%, and 77.7%, respectively. Five mortalities were recorded, including 2 cases of anal cancer, 2 CD-related complications, and one case of pneumonia. CONCLUSION: Over 40% of CD patients presented with perianal disease at diagnosis. Patients with PCD had poor outcome, with young age of onset, multiple antibiotic use, and repeated surgery.