There is a need for an improved biomarker for colorectal cancer (CRC) and advanced adenoma. We evaluated faecal microbial markers for clinical use in detecting CRC and advanced adenoma.
We measured ...relative abundance of
(
),
(
) and
(
) by quantitative PCR in 309 subjects, including 104 patients with CRC, 103 patients with advanced adenoma and 102 controls. We evaluated the diagnostic performance of these biomarkers with respect to faecal immunochemical test (FIT), and validated the results in an independent cohort of 181 subjects.
The abundance was higher for all three individual markers in patients with CRC than controls (p<0.001), and for marker
in patients with advanced adenoma than controls (p=0.022). The marker
, when combined with FIT, showed superior sensitivity (92.3% vs 73.1%, p<0.001) and area under the receiver-operating characteristic curve (AUC) (0.95 vs 0.86, p<0.001) than stand-alone FIT in detecting CRC in the same patient cohort. This combined test also increased the sensitivity (38.6% vs 15.5%, p<0.001) and AUC (0.65 vs 0.57, p=0.007) for detecting advanced adenoma. The performance gain for both CRC and advanced adenoma was confirmed in the validation cohort (p=0.0014 and p=0.031, respectively).
This study identified marker
as a valuable marker to improve diagnostic performance of FIT, providing a complementary role to detect lesions missed by FIT alone. This simple approach may improve the clinical utility of the current FIT, and takes one step further towards a non-invasive, potentially more accurate and affordable diagnosis of advanced colorectal neoplasia.
Abstract
Background
Increased inflammation has been well defined in coronavirus disease 2019 (COVID-19), while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils ...are known to contribute to immunopathology in infections, inflammatory diseases, and acute respiratory distress syndrome, a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets.
Methods
Blood was obtained serially from critically ill COVID-19 patients for 11 days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis, and cytokine levels were assessed. Lung tissue was obtained immediately postmortem for immunostaining. PubMed searches for neutrophils, lung, and COVID-19 yielded 10 peer-reviewed research articles in English.
Results
Elevations in neutrophil-associated cytokines interleukin 8 (IL-8) and interleukin 6, and general inflammatory cytokines IFN-inducible protien-19, granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin 1β, interleukin 10, and tumor necrosis factor, were identified both at first measurement and across hospitalization (P < .0001). COVID-19 neutrophils had exaggerated oxidative burst (P < .0001), NETosis (P < .0001), and phagocytosis (P < .0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–infected lungs available for examination (2 of 5). While elevations in IL-8 and absolute neutrophil count correlated with disease severity, plasma IL-8 levels alone correlated with death.
Conclusions
Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. Importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data show that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.
Neutrophils in the circulation of critically ill COVID-19 patients with acute respiratory distress syndrome have functional changes over the course of their disease. These neutrophils have increased antimicrobial and proinflammatory functionality, including neutrophil extracellular trap formation, phagocytosis, and oxidative burst.
Artificial intelligence (AI)–assisted colonoscopy improves polyp detection and characterization in colonoscopy. However, data from large-scale multicenter randomized controlled trials (RCT) in an ...asymptomatic population are lacking.
This multicenter RCT aimed to compare AI-assisted colonoscopy with conventional colonoscopy for adenoma detection in an asymptomatic population. Asymptomatic subjects 45–75 years of age undergoing colorectal cancer screening by direct colonoscopy or fecal immunochemical test were recruited in 6 referral centers in Hong Kong, Jilin, Inner Mongolia, Xiamen, and Beijing. In the AI-assisted colonoscopy, an AI polyp detection system (Eagle-Eye) with real-time notification on the same monitor of the endoscopy system was used. The primary outcome was overall adenoma detection rate (ADR). Secondary outcomes were mean number of adenomas per colonoscopy, ADR according to endoscopist’s experience, and colonoscopy withdrawal time. This study received Institutional Review Board approval (CRE-2019.393).
From November 2019 to August 2021, 3059 subjects were randomized to AI-assisted colonoscopy (n = 1519) and conventional colonoscopy (n = 1540). Baseline characteristics and bowel preparation quality between the 2 groups were similar. The overall ADR (39.9% vs 32.4%; P < .001), advanced ADR (6.6% vs 4.9%; P = .041), ADR of expert (42.3% vs 32.8%; P < .001) and nonexpert endoscopists (37.5% vs 32.1%; P = .023), and adenomas per colonoscopy (0.59 ± 0.97 vs 0.45 ± 0.81; P < .001) were all significantly higher in the AI-assisted colonoscopy. The median withdrawal time (8.3 minutes vs 7.8 minutes; P = .004) was slightly longer in the AI-assisted colonoscopy group.
In this multicenter RCT in asymptomatic patients, AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists. (ClinicalTrials.gov, Number: NCT04422548).
The number of artificial intelligence (AI) studies in medicine has exponentially increased recently. However, there is no clear quantification of the clinical benefits of implementing AI-assisted ...tools in patient care.
This study aims to systematically review all published randomized controlled trials (RCTs) of AI-assisted tools to characterize their performance in clinical practice.
CINAHL, Cochrane Central, Embase, MEDLINE, and PubMed were searched to identify relevant RCTs published up to July 2021 and comparing the performance of AI-assisted tools with conventional clinical management without AI assistance. We evaluated the primary end points of each study to determine their clinical relevance. This systematic review was conducted following the updated PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines.
Among the 11,839 articles retrieved, only 39 (0.33%) RCTs were included. These RCTs were conducted in an approximately equal distribution from North America, Europe, and Asia. AI-assisted tools were implemented in 13 different clinical specialties. Most RCTs were published in the field of gastroenterology, with 15 studies on AI-assisted endoscopy. Most RCTs studied biosignal-based AI-assisted tools, and a minority of RCTs studied AI-assisted tools drawn from clinical data. In 77% (30/39) of the RCTs, AI-assisted interventions outperformed usual clinical care, and clinically relevant outcomes improved with AI-assisted intervention in 70% (21/30) of the studies. Small sample size and single-center design limited the generalizability of these studies.
There is growing evidence supporting the implementation of AI-assisted tools in daily clinical practice; however, the number of available RCTs is limited and heterogeneous. More RCTs of AI-assisted tools integrated into clinical practice are needed to advance the role of AI in medicine.
PROSPERO CRD42021286539; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=286539.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
We validated a modified risk algorithm based on the Asia-Pacific Colorectal Screening (APCS) score that included body mass index (BMI) for prediction of advanced neoplasia.
Among 5744 Chinese ...asymptomatic screening participants undergoing a colonoscopy in Hong Kong from 2008 to 2012, a random sample of 3829 participants acted as the derivation cohort. The odds ratios for significant risk factors identified by binary logistic regression analysis were used to build a scoring system ranging from 0 to 6, divided into "average risk" (AR): 0; "moderate risk" (MR): 1-2; and "high risk" (HR): 3-6. The other 1915 subjects formed a validation cohort, and the performance of the score was assessed.
The prevalence of advanced neoplasia in the derivation and validation cohorts was 5.4% and 6.0%, respectively (P = 0.395). Old age, male gender, family history of colorectal cancer, smoking, and BMI were significant predictors in multivariate regression analysis. A BMI cut-off at > 23 kg/m
had better predictive capability and lower number needed to screen than that of > 25 kg/m
. Utilizing the score developed, 8.4%, 57.4%, and 34.2% in the validation cohort were categorized as AR, MR, and HR, respectively. The corresponding prevalence of advanced neoplasia was 3.8%, 4.3%, and 9.3%. Subjects in the HR group had 2.48-fold increased prevalence of advanced neoplasia than the AR group. The c-statistics of the modified score had better discriminatory capability than that using predictors of APCS alone (c-statistics = 0.65 vs 0.60).
Incorporating BMI into the predictors of APCS score was found to improve risk prediction of advanced neoplasia and reduce colonoscopy resources.
We tested the a priori hypothesis that self-perceived and real presences of risks for colorectal cancer (CRC) are associated with better knowledge of the symptoms and risk factors for CRC, ...respectively.
One territory-wide invitation for free CRC screening between 2008 to 2012 recruited asymptomatic screening participants aged 50-70 years in Hong Kong. They completed survey items on self-perceived and real presences of risks for CRC (advanced age, male gender, positive family history and smoking) as predictors, and knowledge of CRC symptoms and risk factors as outcome measures, respectively. Their associations were evaluated by binary logistic regression analyses.
From 10,078 eligible participants (average age 59 years), the mean knowledge scores for symptoms and risk factors were 3.23 and 4.06, respectively (both score range 0-9). Male gender (adjusted odds ratio AOR = 1.34, 95% C.I. 1.20-1.50, p<0.01), self-perception as not having any risks for CRC (AOR = 1.12, 95% C.I. 1.01-1.24, p = 0.033) or uncertainty about having risks (AOR = 1.94, 95% C.I. 1.55-2.43, p<0.001), smoking (AOR 1.38, 95% C.I. 1.11-1.72, p = 0.004), and the absence of family history (AOR 0.61 to 0.78 for those with positive family history, p<0.001) were associated with poorer knowledge scores (≤ 4) of CRC symptoms. These factors remained significant for knowledge of risk factors.
Male and smokers were more likely to have poorer knowledge but family history of CRC was associated with better knowledge. Since screening of these higher risk individuals could lead to greater yield of colorectal neoplasm, educational interventions targeted to male smokers were recommended.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Stress hyperglycemia is associated with an increased risk of diabetes among survivors of critical illness. We investigated whether patients without diabetes hospitalized for bacteremia or ...nonbacteremic diseases with transient stress hyperglycemia would have a higher risk of subsequent diabetes development compared with those who remained normoglycemic.
This retrospective observational study was conducted on 224,534 in-patients with blood culture records. Stress hyperglycemia was defined based on the highest random glucose level ≥7.8 mmol/L during the index admission period. Diagnosis of diabetes, as the primary end point of interest, was defined based on diagnostic codes, blood test results, or medication records. Differences in cumulative incidence and hazard ratios (HRs) of diabetes between groups were assessed using the Kaplan-Meier estimator and Cox regression.
After exclusion of patients with preexisting or undiagnosed diabetes or indeterminate diabetes status and propensity score matching, bacteremic patients with stress hyperglycemia had a significantly higher cumulative incidence of diabetes (HR 1.7, 95% CI 1.2-2.4) compared with those who remained normoglycemic. Stress hyperglycemia was further confirmed to be a diabetes predictor independent of age, sex, comorbidity, and other serological markers. For the nonbacteremic patients, stress hyperglycemia was similarly associated with a higher cumulative incidence of diabetes (HR 1.4, 95% CI 1.2-1.7).
Hospitalized patients with transient stress hyperglycemia had a higher risk of subsequent diabetes development compared with their normoglycemic counterparts. Recognition of an increased risk of diabetes in these patients can allow early detection and monitoring in their subsequent follow-ups.
to evaluate the proportion of self-referred screening participants having various psychological barriers and the factors associated with these barriers.
A territory-wide bowel cancer screening centre ...sent an invitation via the media to all Hong Kong residents aged 50-70 years who were asymptomatic of CRC to join a free screening programme. Upon attendance they were requested to complete self-administered surveys on their perceived barriers of screening. Binary logistic regression analyses were used to evaluate the factors associated with these barriers.
From 10,078 consecutive screening participants (mean age 57.5 years; female 56.4%) completed the surveys between May 2008 to September 2012. There were high proportions who agreed or strongly agreed with the following barriers: financial difficulty (86.0%), limited service accessibility (58.2%), screening-induced bodily discomfort (55.2%), physical harm (44.4%), embarrassment (40.1%), apprehension (38.8%) and time constraints (13.9%). From regression models, older participants (aged ≥ 56) were less likely to have these barriers (Adjusted odds ratio AOR ranged from 0.738 to 0.952) but they encountered more difficulties to access to screening services (AOR ranged from 1.141 to 1.371). Female subjects were more likely to encounter most of these barriers (AOR ranged from 1.188 to 2.179). Participants who were uncertain of the necessity of CRC screening for people aged ≥ 50 were more likely to report these barriers (AOR ranged from 1.151 to 1.671).
The proportions of perceptual barriers of CRC screening were high among these participants. Those with these associated factors should receive more thorough explanation of the screening test procedures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract Objective This study aims to examine the rate and determinants of faecal immunochemical test (FIT) compliance over a four-year period among asymptomatic participants in a colorectal cancer ...(CRC) screening programme in Hong Kong. Method Self-referred screening participants aged between 50 and 70 years who chose FIT for annual screening were followed up for four years (2008–2012). All participants were reminded up to three times yearly for FIT retrieval within two months of the expected screening date. The proportions of screening participants who failed to adhere to annual FIT tests in 1, 2, 3 and 4-years, respectively, after the initial screening uptake were evaluated. The factors associated with non-compliance with FITs in any year were assessed by a binary logistic regression analysis. Results From 5700 consecutive screening participants, the compliance rates to FIT were 95.1%, 79.9%, 66.2% and 68.4% at years one to four, respectively. The proportions of people missing one, two and three tests were 6.2%, 19.6% and 2.1%, respectively. From multivariate regression analysis, male subjects, younger participants, smokers and those with positive family history of CRC were more likely to be non-compliant. Conclusion Participants identified as at higher risk for screening non-compliance should be especially considered for individual reminders to enhance screening effectiveness.
Using prostate-specific antigen (PSA) for prostate cancer (PCa) screening led to overinvestigation and overdiagnosis of indolent PCa. We aimed to investigate the value of prostate health index (PHI) ...and magnetic resonance imaging (MRI) prostate in an Asian PCa screening program. Men aged 50-75 years were prospectively recruited from a community-based PSA screening program. Men with PSA 4.0-10.0 ng ml−1 had PHI result analyzed. MRI prostate was offered to men with PSA 4.0-50.0 ng ml−1. A systematic prostate biopsy was offered to men with PSA 4.0-9.9 ng ml−1 and PHI ≥35, or PSA 10.0-50.0 ng ml−1. Additional targeted prostate biopsy was offered if they had PI-RADS score ≥3. Clinically significant PCa (csPCa) was defined as the International Society of Urological Pathology (ISUP) grade group (GG) ≥2 or ISUP GG 1 with involvement of ≥30% of total systematic cores. In total, 12.8% (196/1536) men had PSA ≥4.0 ng ml−1. Among 194 men with PSA 4.0-50.0 ng ml−1, 187 (96.4%) received MRI prostate. Among them, 28.3% (53/187) had PI-RADS ≥3 lesions. Moreover, 7.0% (107/1536) men were indicated for biopsy and 94.4% (101/107) men received biopsy. Among the men received biopsy, PCa, ISUP GG ≥2 PCa, and csPCa was diagnosed in 42 (41.6%), 24 (23.8%), and 34 (33.7%) men, respectively. Compared with PSA/PHI pathway in men with PSA 4.0-50.0 ng ml−1, additional MRI increased diagnoses of PCa, ISUP GG ≥2 PCa, and csPCa by 21.2% (from 33 to 40), 22.2% (from 18 to 22), and 18.5% (from 27 to 32), respectively. The benefit of additional MRI was only observed in PSA 4.0-10.0 ng ml−1, and the number of MRI needed to diagnose one additional ISUP GG ≥2 PCa was 20 in PHI ≥35 and 94 in PHI <35. Among them, 45.4% (89/196) men with PSA ≥4.0 ng ml−1 avoided unnecessary biopsy with the use of PHI and MRI. A screening algorithm with PSA, PHI, and MRI could effectively diagnose csPCa while reducing unnecessary biopsies. The benefit of MRI prostate was mainly observed in PSA 4.0-9.9 ng ml−1 and PHI ≥35 group. PHI was an important risk stratification step for PCa screening.
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