Optimal glycaemic control and the reduced risk of colorectal adenoma and cancer in patients with diabetes: a population-based cohort study.

OBJECTIVE: Whether varying degrees of glycaemic control impact colonic neoplasm risk in patients with diabetes mellitus (DM) remains uncertain. DESIGN: Patients with newly diagnosed DM were retrieved from 2005 to 2013. Optimal glycaemic control at baseline was defined as mean haemoglobin A1c (HbA1c)<7%. Outcomes of interest included colorectal cancer (CRC) and colonic adenoma development. We used propensity score (PS) matching with competing risk models to estimate subdistribution HRs (SHRs). We further analysed the combined effect of baseline and postbaseline glycaemic control based on time-weighted mean HbA1c during follow-up. RESULTS: Of 88 468 PS-matched patients with DM (mean (SD) age: 61.5 (±11.7) years; male: 47 127 (53.3%)), 1229 (1.4%) patients developed CRC during a median follow-up of 7.2 (IQR: 5.5-9.4) years. Optimal glycaemic control was associated with lower CRC risk (SHR 0.72; 95% CI 0.65 to 0.81). The beneficial effect was limited to left-sided colon (SHR 0.71; 95% CI 0.59 to 0.85) and rectum (SHR 0.71; 95% CI 0.57 to 0.89), but not right-sided colon (SHR 0.86; 95% CI 0.67 to 1.10). Setting suboptimal glycaemic control at baseline/postbaseline as a reference, a decreased CRC risk was found in optimal control at postbaseline (SHR 0.79), baseline (SHR 0.71) and both time periods (SHR 0.61). Similar associations were demonstrated using glycaemic control as a time-varying covariate (HR 0.75). A stepwise greater risk of CRC was found (Ptrend<0.001) with increasing HbA1c (SHRs 1.34, 1.30, 1.44, 1.58 for HbA1c 7.0% to <7.5%, 7.5% to <8.0%, 8.0% to <8.5% and ≥8.5%, respectively). Optimal glycaemic control was associated with a lower risk of any, non-advanced and advanced colonic adenoma (SHRs 0.73-0.87). CONCLUSION: Glycaemic control in patients with DM was independently associated with the risk of colonic adenoma and CRC development with a biological gradient.

RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates.

At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.

IL-1ß and TNF-α play an important role in modulating the risk of periodontitis and Alzheimer's disease.

BACKGROUND: Systemic activation of the immune system can exert detrimental effects on the central nervous system. Periodontitis, a chronic disease of the oral cavity, is a common source of systemic inflammation. Neuroinflammation might be a result of this to accelerate progressive deterioration of neuronal functions during aging or exacerbate pre-existing neurodegenerative diseases, such as Alzheimer's disease. With advancing age, the progressive increase in the body's pro-inflammatory status favors the state of vulnerability to both periodontitis and Alzheimer's disease. In the present study, we sought to delineate the roles of cytokines in the pathogenesis of both diseases. METHODS: To examine the impacts of periodontitis on the onset and progression of Alzheimer's disease, 6-month-old female 3 × Tg-AD mice and their age-matched non-transgenic mice were employed. Periodontitis was induced using two different experimental models: heat-killed bacterial-induced periodontitis and ligature-induced periodontitis. To delineate the roles of pro-inflammatory cytokines in the pathogenesis of periodontitis and Alzheimer's disease, interleukin 1 beta (IL-1ß) and tumor necrosis factor-alpha (TNF-α) were also injected into the buccal mandibular vestibule of mice. RESULTS: Here, we show that IL-1ß and TNF-α were two of the most important and earliest cytokines upregulated upon periodontal infection. The systemic upregulation of these two cytokines promoted a pro-inflammatory environment in the brain contributing to the development of Alzheimer's disease-like pathology and cognitive dysfunctions. Periodontitis-induced systemic inflammation also enhanced brain inflammatory responses and subsequently exacerbated Alzheimer's disease pathology and cognitive impairment in 3 × Tg-AD mice. The role of inflammation in connecting periodontitis to Alzheimer's disease was further affirmed in the conventional magnetization transfer experiment in which increased glial responses resulting from periodontitis led to decreased magnetization transfer ratios in the brain of 3 × Tg-AD mice. CONCLUSIONS: Systemic inflammation resulting from periodontitis contributed to the development of Alzheimer's disease tau pathology and subsequently led to cognitive decline in non-transgenic mice. It also potentiated Alzheimer's disease pathological features and exacerbated impairment of cognitive function in 3 × Tg-AD mice. Taken together, this study provides convincing evidence that systemic inflammation serves as a connecting link between periodontitis and Alzheimer's disease.

The Impacts of Computer-Aided Detection of Colorectal Polyps on Subsequent Colonoscopy Surveillance Intervals: Simulation Study.

BACKGROUND: Computer-aided detection (CADe) of colorectal polyps has been shown to increase adenoma detection rates, which would potentially shorten subsequent surveillance intervals. OBJECTIVE: The purpose of this study is to simulate the potential changes in subsequent colonoscopy surveillance intervals after the application of CADe in a large cohort of patients. METHODS: We simulated the projected increase in polyp and adenoma detection by universal CADe application in our patients who had undergone colonoscopy with complete endoscopic and histological findings between 2016 and 2020. The simulation was based on bootstrapping the published performance of CADe. The corresponding changes in surveillance intervals for each patient, as recommended by the US Multi-Society Task Force on Colorectal Cancer (USMSTF) or the European Society of Gastrointestinal Endoscopy (ESGE), were determined after the CADe was determined. RESULTS: A total of 3735 patients who had undergone colonoscopy were included. Based on the simulated CADe effect, the application of CADe would result in 19.1% (n=714) and 1.9% (n=71) of patients having shorter surveillance intervals, according to the USMSTF and ESGE guidelines, respectively. In particular, all (or 2.7% (n=101) of the total) patients who were originally scheduled to have 3-5 years of surveillance would have their surveillance intervals shortened to 3 years, following the USMSTF guidelines. The changes in this group of patients were largely attributed to an increase in the number of adenomas (n=75, 74%) rather than serrated lesions being detected. CONCLUSIONS: Widespread adoption of CADe would inevitably increase the demand for surveillance colonoscopies with the shortening of original surveillance intervals, particularly following the current USMSTF guideline.

Mass Spectrometry-Based Proteomics for Discovering Salivary Biomarkers in Periodontitis: A Systematic Review.

Periodontitis is one of the primary causes of tooth loss, and is also related to various systemic diseases. Early detection of this condition is crucial when it comes to preventing further oral damage and the associated health complications. This study offers a systematic review of the literature published up to April 2023, and aims to clearly explain the role of proteomics in identifying salivary biomarkers for periodontitis. Comprehensive searches were conducted on PubMed and Web of Science to shortlist pertinent studies. The inclusion criterion was those that reported on mass spectrometry-driven proteomic analyses of saliva samples from periodontitis cohorts, while those on gingivitis or other oral diseases were excluded. An assessment for risk of bias was carried out using the Newcastle-Ottawa Scale and Quality Assessment of Diagnostic Accuracy Studies or the NIH quality assessment tool, and a meta-analysis was performed for replicable candidate biomarkers, i.e., consistently reported candidate biomarkers (in specific saliva samples, and periodontitis subgroups, reported in ≥2 independent cohorts/reports) were identified. A Gene Ontology enrichment analysis was conducted using the Database for Annotation, Visualization, and Integrated Discovery bioinformatics resources, which consistently expressed candidate biomarkers, to explore the predominant pathway wherein salivary biomarkers consistently manifested. Of the 15 studies included, 13 were case-control studies targeting diagnostic biomarkers for periodontitis participants (periodontally healthy/diseased, n = 342/432), while two focused on biomarkers responsive to periodontal treatment (n = 26 participants). The case-control studies were considered to have a low risk of bias, while the periodontitis treatment studies were deemed fair. Summary estimate and confidence/credible interval, etc. determination for the identified putative salivary biomarkers could not be ascertained due to the low number of studies in each case. The results from the included case-control studies identified nine consistently expressed candidate biomarkers (from nine studies with 230/297 periodontally healthy/diseased participants): (i) those that were upregulated: alpha-amylase, serum albumin, complement C3, neutrophil defensin, profilin-1, and S100-P; and (ii) those that were downregulated: carbonic anhydrase 6, immunoglobulin J chain, and lactoferrin. All putative biomarkers exhibited consistent regulation patterns. The implications of the current putative marker proteins identified were reviewed, with a focus on their potential roles in periodontitis diagnosis and pathogenesis, and as putative therapeutic targets. Although in its early stages, mass spectrometry-based salivary periodontal disease biomarker proteomics detection appeared promising. More mass spectrometry-based proteomics studies, with or without the aid of already available clinical biochemical approaches, are warranted to aid the discovery, identification, and validation of periodontal health/disease indicator molecule(s). Protocol registration number: CRD42023447722; supported by RD-02-202410 and GRF17119917.

Serum microRNA Levels as a Biomarker for Diagnosing Non-Alcoholic Fatty Liver Disease in Chinese Colorectal Polyp Patients.

Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases and its prevalence is increasing worldwide. It is reported that NAFLD is associated with colorectal polyps. Since identifying NAFLD in its early stages could prevent possible disease progression to cirrhosis and decrease the risk of HCC by early intervention, patients with colorectal polyp may thus be considered a target group for screening NAFLD. This study aimed to investigate the potential of serum microRNAs (miRNAs) in identifying NAFLD for colorectal polyp patients. Serum samples were collected from 141 colorectal polyp patients, of which 38 had NAFLD. The serum level of eight miRNAs was determined by quantitative PCR and delta Ct values of different miRNA pairs which were compared between NAFLD and control groups. A miRNA panel was formulated from candidate miRNA pairs by multiple linear regression model and ROC analysis was performed to evaluate its diagnostic potential for NAFLD. Compared to the control group, the NAFLD group showed significantly lower delta Ct values of miR-18a/miR-16 (6.141 vs. 7.374, p = 0.009), miR-25-3p/miR-16 (2.311 vs. 2.978, p = 0.003), miR-18a/miR-21-5p (4.367 vs. 5.081, p = 0.021) and miR-18a/miR-92a-3p (8.807 vs. 9.582, p = 0.020). A serum miRNA panel composed of these four miRNA pairs significantly identified NAFLD in colorectal polyp patients with an AUC value of 0.6584 (p = 0.004). The performance of the miRNA panel was further improved to an AUC value of 0.8337 (p < 0.0001) when polyp patients with other concurrent metabolic disorders were removed from the analysis. The serum miRNA panel is a potential diagnostic biomarker for screening NAFLD in colorectal polyp patients. This serum miRNA test could be performed for colorectal polyp patients for early diagnosis and for prevention of the disease from progressing into more advanced stages.

Adjunctive Er:YAG laser in non-surgical periodontal therapy of patients with inadequately controlled type 2 diabetes mellitus: A split-mouth randomized controlled study.

BACKGROUND AND OBJECTIVE: Limited studies are available comparing the outcomes of non-surgical periodontal therapy (NSPT) with or without adjunctive Er:YAG laser (ERL) in patients with type 2 diabetes mellitus (T2DM). This study evaluated the effects of ERL adjunctive NSPT on single-rooted teeth of inadequately controlled T2DM patients with periodontitis. METHODS: Twenty-two inadequately controlled T2DM participants with periodontitis were recruited. Adopting a double-blinded split-mouth design and under block randomization, we investigated the effects of ERL in calculus removal then degranulation mode, or a sham treatment, adjunct NSPT, which included two visits of full-mouth root surface debridement delivered within 4-10 days, to test or control single-rooted teeth (Wuxi Stomatology Hospital, trial 2017-016). We followed periodontal parameters (plaque %, bleeding on probing [BOP] %, probing pocket depth [PPD], probing attachment level [PAL]) and selected systemic parameters (fasting plasma glucose [FPG], glycosylated hemoglobin [HbA1c%], high sensitivity C-reactive protein) at baseline, one, three, and six months after periodontal treatment. RESULTS: The study was completed as planned. Periodontal parameters, FPG and HbA1c% of the 22 participants appeared significantly improved at six months (p < 0.001). The 44 ERL treated, compared to 44 sham treated single-rooted teeth exhibited significant improvement in BOP, mean PPD, and mean PAL at various postoperative follow-up time points (effect size ≥0.44; p < 0.001). No adverse event was reported. CONCLUSION: Periodontal treatment outcomes in the T2DM patients with inadequate glycemic control were better in the single-rooted teeth received ERL adjunct NSPT. Further studies are warranted to confirm the observations reported in this short-term clinical study.

Facial profile study using 3-dimensional photographs to assess esthetic preferences of Hong Kong Chinese orthognathic patients and laypersons.

INTRODUCTION: This study was conducted to investigate and compare esthetic perceptions of different facial profiles among Hong Kong Chinese laypersons and patients scheduled for orthognathic treatment. METHODS: Two sets of 3-dimensional facial photographs (1 male and 1 female) each comprised 7 images that showed different dentoskeletal relations (ie, Class I, bimaxillary protrusion, bimaxillary retrusion, maxillary protrusion, maxillary retrusion, mandibular protrusion, and mandibular retrusion). The sets of photographs were shown to 101 laypersons (age, 28.87 ± 6.22 years) and 60 patients seeking orthognathic treatment (age, 27.12 ± 6.07 years). They rated their esthetic perceptions of the photographs on the basis of a 100 mm visual analog scale (VAS) from 0 (very unattractive) to 100 (very attractive). RESULTS: The dentoskeletal Class I facial profile was ranked as the most attractive profile. Female orthognathic judges selected the retrusive maxilla while male orthognathic judges and male and female laypersons ranked the mandibular protrusion profile as the least attractive profile for both females and males. A bimaxillary protrusive female profile was viewed as more attractive by the orthognathic male (P = 0.006) and female (P = 0.006) judges, compared with female layperson judges. After adjustment for age, no statistically significant interaction between sex and judges (P >0.10) for all VAS scores were detected. For the female bimaxillary protrusive profile, orthognathic patient judges assigned a mean VAS score of 9.174 points higher than layperson judges (95% confidence interval, 3.11-15.24; P = 0.003). CONCLUSION: Dentoskeletal Class I facial profile was generally considered the most attractive profile in both sexes; male and female orthognathic patients preferred a bimaxillary protrusive female profile. A concave facial profile was perceived as least attractive in both sexes.

Calcium channel blockers are associated with lower gastric cancer risk: A territory-wide study with propensity score analysis.

Prior studies showed that calcium channel blockers (CCBs) could modify cancer risk, but data on gastric cancer (GC) are limited. We aimed to investigate whether CCBs could modify GC risk in Helicobacter pylori-eradicated patients. H pylori-infected patients with hypertension who are aged ≥50 and had received clarithromycin-based triple therapy between 2003 and 2016 were identified from a territory-wide healthcare database. Patients with eradication failure, GC diagnosed within 6 months after HP eradication, and gastric ulcer were excluded. Time-fixed Cox model with one-to-one propensity score matching was used to calculate hazard ratio (HR) of GC with CCBs. Sensitivity analysis using time-dependent multivariable Cox model in which CCB use was treated as time-varying covariate was also performed to address immortal time bias. 17 622 (29.6%) H pylori-eradicated patients with hypertension were included. During a median follow-up of 8.6 years, 105 (0.6%) developed GC. After PS matching, CCBs were associated with a lower GC risk (HR: 0.56; 95% CI: 0.32-0.97). Time-dependent analysis showed consistent result (aHR: 0.50; 95% CI: 0.33-0.75). A longer duration of CCB use was associated with even lower GC risk (adjusted HR [aHR]: 0.69; 95% CI: 0.61-0.79 for every 1-year increase in use). Long-acting CCBs (aHR: 0.47; 95% CI: 0.29-0.76) and dihydropyridines (aHR: 0.49; 95% CI: 0.32-0.73) conferred greater benefit than short-acting ones (aHR: 0.60; 95% CI: 0.36-1.03) and nondihydropyridines (aHR: 0.76; 95% CI: 0.24-2.48). The aHR was 0.57 (95% CI: 0.34-0.97) for noncardia and 0.59 (95% CI: 0.27-1.31) for cardia cancer. Use of CCBs was associated with lower risk of GC development in H pylori-eradicated patients, in a duration- and dose-response manner.

Nonaspirin nonsteroidal anti-inflammatory drugs and gastric cancer risk after Helicobacter pylori eradication: A territory-wide study.

BACKGROUND: Despite Helicobacter pylori (HP) eradication, individuals can still develop gastric cancer (GC). Prior studies have demonstrated that nonaspirin nonsteroidal anti-inflammatory drugs (NA-NSAIDs) reduce the risk of GC, but this may be caused by immortal time bias and failure to adjust for HP status. The objective of this study was to investigate whether NA-NSAIDs reduced the risk of GC in patients who undergo H. pylori eradication. METHODS: Adult patients who had received clarithromycin-based triple therapy between 2003 and 2016 were identified from a territory-wide health care database. Exclusion criteria included prior GC or GC diagnosed <6 months after HP eradication, prior gastrectomy, gastric ulcer after HP eradication, and failure of triple therapy. Covariates included age, sex, prior peptic ulcer disease, other comorbidities, and concurrent medications (aspirin, proton pump inhibitors, statins, and metformin). To avoid immortal time bias, NA-NSAID use (≥90 days) was treated as a time-dependent variable in a multivariable Cox model (time-dependent analysis). Time-independent analysis was also performed. RESULTS: During a median follow-up of 8.9 years (interquartile range, 5.4-12.6 years), 364 of 92,017 patients (0.4%) who underwent HP eradication developed GC. NA-NSAID use was associated with a significant reduction in the risk of GC in time-fixed analysis (adjusted hazard ratio [aHR], 0.65; 95% CI, 0.47-0.90), but not in time-dependent multivariable analysis (aHR, 1.35; 95% CI, 0.97-1.87). Time-dependent subgroup analyses also did not indicate any significant association between NA-NSAID use and either cardia GC (aHR, 0.75; 95% CI, 0.27-2.06) or noncardia GC (aHR, 1.28; 95% CI, 0.83-1.98). CONCLUSIONS: NA-NSAID use was not associated with a reduced risk of GC among patients who underwent HP eradication. The chemopreventive effect of NA-NSAIDs observed in prior studies may have been confounded by immortal time bias.

Asian Organization for Crohn's and Colitis and Asia Pacific Association of Gastroenterology practice recommendations for medical management and monitoring of inflammatory bowel disease in Asia.

Inflammatory bowel disease (IBD) has increased in incidence and prevalence in Asian countries since the end of the 20th century. Moreover, differences in the cause, phenotypes, and natural history of IBD between the East and West have been recognized. Therefore, the Asian Organization for Crohn's and Colitis and the Asia Pacific Association of Gastroenterology have established recommendations on medical management of IBD in Asia. Initially, the committee members drafted 40 recommendations, which were then assessed according to Grading of Recommendations Assessment, Development and Evaluation. Eight statements were rejected as this indicated that consensus had not been reached. The recommendations encompass pretreatment evaluation; medical management of active IBD; medical management of IBD in remission; management of IBD during the periconception period and pregnancy; surveillance strategies for colitis-associated cancer; monitoring side effects of thiopurines and methotrexate; and infections in IBD.

Narrow-Band Imaging for Detection of Neoplasia at Colonoscopy: A Meta-analysis of Data From Individual Patients in Randomized Controlled Trials.

BACKGROUND & AIMS: Adenoma detection rate (ADR) is an important quality assurance measure for colonoscopy. Some studies suggest that narrow-band imaging (NBI) may be more effective at detecting adenomas than white-light endoscopy (WLE) when bowel preparation is optimal. We conducted a meta-analysis of data from individual patients in randomized controlled trials that compared the efficacy of NBI to WLE in detection of adenomas. METHODS: We searched MEDLINE, EMBASE, and Cochrane Library databases through April 2017 for randomized controlled trials that assessed detection of colon polyps by high-definition WLE vs NBI and from which data on individual patients were available. The primary outcome measure was ADR adjusted for bowel preparation quality. Multilevel regression models were used with patients nested within trials, and trial included as a random effect. RESULTS: We collected data from 11 trials, comprising 4491 patients and 6636 polyps detected. Adenomas were detected in 952 of 2251 (42.3%) participants examined by WLE vs 1011 of 2239 (45.2%) participants examined by NBI (unadjusted odds ratio [OR] for detection of adenoma by WLE vs NBI, 1.14; 95% CI, 1.01-1.29; P = .04). NBI outperformed WLE only when bowel preparation was best: adequate preparation OR, 1.07 (95% CI, 0.92-1.24; P = .38) vs best preparation OR, 1.30 (95% CI, 1.04-1.62; P = .02). Second-generation bright NBI had a better ADR than WLE (second-generation NBI OR, 1.28; 95% CI, 1.05-1.56; P = .02), whereas first-generation NBI did not. NBI detected more non-adenomatous polyps than WLE (OR, 1.24; 95% CI, 1.06-1.44; P = .008) and flat polyps than WLE (OR, 1.24; 95% CI, 1.02-1.51; P = .03). CONCLUSIONS: In a meta-analysis of data from individual patients in randomized controlled trials, we found NBI to have a higher ADR than WLE, and that this effect is greater when bowel preparation is optimal.

Personal Protective Equipment for Endoscopy in Low-Resource Settings During the COVID-19 Pandemic: Guidance From the World Gastroenterology Organisation.

Performance of endoscopic procedures is associated with a risk of infection from COVID-19. This risk can be reduced by the use of personal protective equipment (PPE). However, shortage of PPE has emerged as an important issue in managing the pandemic in both traditionally high and low-resource areas. A group of clinicians and researchers from thirteen countries representing low, middle, and high-income areas has developed recommendations for optimal utilization of PPE before, during, and after gastrointestinal endoscopy with particular reference to low-resource situations. We determined that there is limited flexibility with regard to the utilization of PPE between ideal and low-resource settings. Some compromises are possible, especially with regard to PPE use, during endoscopic procedures. We have, therefore, also stressed the need to prevent transmission of COVID-19 by measures other than PPE and to conserve PPE by reduction of patient volume, limiting procedures to urgent or emergent, and reducing the number of staff and trainees involved in procedures. This guidance aims to optimize utilization of PPE and protection of health care providers.

Cancer risk and chemoprevention in Chinese inflammatory bowel disease patients: a population-based cohort study.

Background and aim: Role of 5-aminosalicylic acid (5-ASA), statin and aspirin in reducing cancer risks in inflammatory bowel disease (IBD) remains controversial. We aimed to examine chemo-preventive effects of these drugs in all cancers in IBD in population-based setting.Methods: IBD patients diagnosed between 2000 and 2016 were identified from the Hong Kong IBD Registry and followed from IBD diagnosis until first cancer occurrence. Primary outcome was cancer development ≥6 months after IBD diagnosis. Adjusted hazard ratio (aHR) with 95% confidence interval (CI) was estimated with Cox proportional hazards model. Additional effects of statin and aspirin on chemoprevention were also assessed.Results: Amongst 2103 IBD patients (857 Crohn's disease, 1246 ulcerative colitis; mean age 40.0 ± 15.6; 60.3% male) with 16,856 person-years follow-up, 48 patients (2.3%) developed cancer. The 5-r, 10-r and 15-year (95% CI) cumulative incidence of cancer were 1% (0.6 - 1.5%), 2.8 (2.0 - 3.9%) and 4.8 (3.4 - 6.5%), respectively. Total 1891 (89.9%) and 222 (10.6%) patients have received one or more prescriptions of 5-ASA and statin respectively. In multivariable analysis adjusted for age, gender, smoking status, IBD type and use of other medications, use of 5-ASA or statin was not associated with a reduced risk of cancer development (5-ASA: aHR 1.22, 95% CI: 0.60-2.48, p = .593; statin: aHR 0.48, 95% CI: 0.14-1.59, p = .227). Adding aspirin was not associated with a lowered cancer risk (aHR 1.18, 95% CI: 0.32-4.35, p = .799).Conclusion: Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit.Key summaryInflammatory bowel diseases (IBD) including Crohn's disease and ulcerative colitis are associated with increased risk of both intestinal and extra- intestinal cancers.Various medications including 5-aminosalicylate acid (5-ASA), statins and aspirin have been studied for their chemoprevention effects. However, most studies focused on colorectal cancer only and showed conflicting evidence. No studies so far looked at the effects of these medications on all cancer development in IBD.The 5-, 10- and 15-year (95% confidence interval) cumulative incidence of cancer in Chinese IBD patients were 1 (0.6-1.5%), 2.8 (2.0-3.9%) and 4.8 (3.4-6.5%), respectively.Use of 5-ASA was not associated with a lowered cancer risk in Chinese IBD patients. Addition of statin/aspirin provided no additional benefit.

Effects of adjunctive probiotic L. reuteri lozenges on S/RSD outcomes at molar sites with deep pockets.

AIM: To evaluate effects of probiotic Lactobacillus reuteri (L. reuteri) lozenges as an S/RSD adjunct on site-level changes at molars with deep pockets. MATERIALS AND METHODS: 447 molar sites with pockets ≥ 5 mm from a previous randomized clinical trial of adjunctive L. reuteri lozenges for 28 days were analyzed. Multilevel mixed-effect models (MLM) were constructed to analyze site-level outcomes "change in CAL" and "pocket closure" (residual PPD < 5 mm) in placebo and probiotic groups at 90 and 180 days. Possible patient-, tooth-, and site-level predictors were analyzed as fixed-effects. RESULTS: Estimated change in CAL in probiotic (90 day: 0.87 mm, 180 day: 0.68 mm) was greater than placebo treated molar sites (90 day: 0.73 mm, 180 day: 0.66 mm) and the relative risk (RR) of pocket closure in the probiotic group (90 day: 1.7, 180 day: 1.6) was higher as compared to placebo. Furcation involvement and BOP at site predicted significantly worse treatment outcomes. CONCLUSION: As compared to S/RSD with placebo, a 28-day course of adjunctive probiotic L. reuteri lozenges improved CAL change at molar sites with ≥ 5 mm deep pockets and conferred a higher probability of shallow residual pocket depth. Presence of furcation-involvement and bleeding on probing worsened treatment outcomes.

In Vitro Salivary Protein Adsorption Profile on Titanium and Ceramic Surfaces and the Corresponding Putative Immunological Implications.

Immune responses triggered by implant abutment surfaces contributed by surface-adsorbed proteins are critical in clinical implant integration. How material surface-adsorbed proteins relate to host immune responses remain unclear. This study aimed to profile and address the immunological roles of surface-adsorbed salivary proteins on conventional implant abutment materials. Standardized polished bocks (5 × 5 × 1 mm3) were prepared from titanium and feldspathic ceramic. Salivary acquired pellicle formed in vitro was examined by liquid chromatography-tandem mass spectrometry and gene ontology (GO) analysis to identify and characterize the adsorbed proteins. Out of 759 proteins identified from pooled saliva samples, 396 were found to be attached to the two materials tested-369 on titanium and 298 on ceramic, with 281 common to both. GO annotation of immune processes was undertaken to form a protein-protein interaction network, and 14 hub proteins (≥6 interaction partners) (coding genes: B2M, C3, CLU, DEFA1, HSP90AA1, HSP90AB1, LTF, PIGR, PSMA2, RAC1, RAP1A, S100A8, S100A9, and SLP1) were identified as the key proteins connecting multiple (6-9) immune processes. The results offered putative immunological prospects of implant abutment material surface-adsorbed salivary proteins, which could potentially underpin the dynamic nature of implant-mucosal/implant-microbial interactions.

A Systematic Review and Meta-analysis of Clinical, Immunological, and Microbiological Shift in Periodontitis After Nonsurgical Periodontal Therapy With Adjunctive Use of Probiotics.

OBJECTIVES: There is a lack of evidence regarding long-term effects of probiotics as adjuncts to nonsurgical periodontal therapy (NSPT) in the management of periodontitis. Therefore, this systematic review aimed to evaluate the clinical, microbiological, and immunological outcomes of probiotics applied as an adjunct to NSPT with at least 3 months of follow-up. METHODS: Electronic searches of 5 databases were performed. Clinical trials that compared the adjunctive use of probiotics in NSPT with NSPT alone, reporting clinical or immunological or microbiological outcomes, were selected. The primary clinical outcome variables were clinical attachment level (CAL) and probing pocket depth (PPD). Meta-analyses were conducted to evaluate the efficacy of probiotics over different longitudinal intervals. RESULTS: Ten randomized controlled trials were included, and high heterogeneity in methods was noted. Meta-analysis revealed CAL gain, and PPD reduction in the probiotics group was significant at 3 months and 12 months, but no significant difference was noted at 6 months and 9 months. There was no significant difference in periodontal pathogen levels between groups at 3 months. Immunological data were not sufficient for quantitative analysis. Ancillary sensitivity analysis indicated a subset of studies with severe mean baseline PPD (≥5 mm) at baseline showed significant and more CAL gain and PPD reduction at 3 months, with probiotics administration of 2-4 weeks. CONCLUSION: Heterogenous evidence implied a long-term clinical benefit of probiotics as an adjunct to NSPT. Outcomes may be impacted by baseline disease severity. Limited microbiological and immunological data precluded any conclusive findings. Current evidence is insufficient to formulate clinical recommendations.

Systemic inflammation linking chronic periodontitis to cognitive decline.

Persistent inflammation in the systemic immune system can impose detrimental effects on the central nervous system (CNS). Neuroinflammation might be a result of this to accelerate the progressive deterioration of neuronal functions during aging. In this regard, controlling inflammation through delaying and/or preventing chronic inflammatory diseases may be a potential strategy to prevent or modify the progression of Alzheimer's Disease (AD). Periodontitis is a chronic inflammatory disease of the oral cavity that is common among the elderly, especially for those who have decline in cognitive functions. While epidemiological findings support the association of chronic periodontitis and cognitive decline, whether they have causal relationship remains unclear. Nonetheless, the possibility that periodontopathogens, systemic immune cells and inflammatory cytokines could reach the CNS should not be overlooked. The impacts of periodontitis on CNS homeostasis and inflammation as a pathophysiological factor concerning the association between periodontitis and AD will be discussed in this review. Future work should elucidate the pathological pathways involved in periodontitis-induced cerebral infections and inflammation, and define the role of the latter in AD progression.

Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn's disease in Asia.

The Asia-Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, under the auspices of the Asia-Pacific Association of Gastroenterology with the goal of improving inflammatory bowel disease care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn's and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in conjunction with conventional treatments for ulcerative colitis and Crohn's disease in Asia. These statements also address how pharmacogenetics influences the treatments of ulcerative colitis and Crohn's disease and provides guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of inflammatory bowel disease workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing, and future revisions are likely as new data continue to emerge.

A double-blind, paralleled-arm, placebo-controlled and randomized clinical trial of the effectiveness of probiotics as an adjunct in periodontal care.

AIM: This study aimed to evaluate the clinical effectiveness of the probiotic Lactobacillus reuteri as an adjunct to non-surgical periodontal therapy (NSPT). MATERIALS AND METHODS: A double-blind, paralleled-arm, placebo-controlled and randomized clinical trial was conducted. Probiotics L. reuteri or placebo lozenges were randomly prescribed for use twice-daily for 28 days. Primary outcomes were clinical attachment levels (CAL) and probing pocket depths (PPD). All participants underwent NSPT, and follow-up clinical assessments were performed at day 90 and day 180. RESULTS: The trial response rate was 69.5% (41 out of 59). Among the test and control groups, there were significant intra-group differences in primary outcomes: CAL (both, p < .001) and PPD (both, p < .001); and in secondary outcomes: percentage of sites with 'bleeding on probing' (both, p < .001) and visible plaque (both, p < .001). There were no statistically significant inter-group differences in any outcomes at any time points (all, p > .05) nor in the changes in outcomes (∆) with time (all, p > .05). There was a trend of a greater magnitude of statistical change occurring among the test group compared to the control group. CONCLUSION: The adjunctive use of probiotics with NSPT did not show any additional clinical effectiveness when compared to NSPT alone in the management of periodontitis (ChiCTR-IOR-17010526).