Autism-related dietary preferences mediate autism-gut microbiome associations.

There is increasing interest in the potential contribution of the gut microbiome to autism spectrum disorder (ASD). However, previous studies have been underpowered and have not been designed to address potential confounding factors in a comprehensive way. We performed a large autism stool metagenomics study (n = 247) based on participants from the Australian Autism Biobank and the Queensland Twin Adolescent Brain project. We found negligible direct associations between ASD diagnosis and the gut microbiome. Instead, our data support a model whereby ASD-related restricted interests are associated with less-diverse diet, and in turn reduced microbial taxonomic diversity and looser stool consistency. In contrast to ASD diagnosis, our dataset was well powered to detect microbiome associations with traits such as age, dietary intake, and stool consistency. Overall, microbiome differences in ASD may reflect dietary preferences that relate to diagnostic features, and we caution against claims that the microbiome has a driving role in ASD.

Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society.

In the United States, colorectal cancer (CRC) is the fourth most common cancer diagnosed among adults and the second leading cause of death from cancer. For this guideline update, the American Cancer Society (ACS) used an existing systematic evidence review of the CRC screening literature and microsimulation modeling analyses, including a new evaluation of the age to begin screening by race and sex and additional modeling that incorporates changes in US CRC incidence. Screening with any one of multiple options is associated with a significant reduction in CRC incidence through the detection and removal of adenomatous polyps and other precancerous lesions and with a reduction in mortality through incidence reduction and early detection of CRC. Results from modeling analyses identified efficient and model-recommendable strategies that started screening at age 45 years. The ACS Guideline Development Group applied the Grades of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria in developing and rating the recommendations. The ACS recommends that adults aged 45 years and older with an average risk of CRC undergo regular screening with either a high-sensitivity stool-based test or a structural (visual) examination, depending on patient preference and test availability. As a part of the screening process, all positive results on noncolonoscopy screening tests should be followed up with timely colonoscopy. The recommendation to begin screening at age 45 years is a qualified recommendation. The recommendation for regular screening in adults aged 50 years and older is a strong recommendation. The ACS recommends (qualified recommendations) that: 1) average-risk adults in good health with a life expectancy of more than 10 years continue CRC screening through the age of 75 years; 2) clinicians individualize CRC screening decisions for individuals aged 76 through 85 years based on patient preferences, life expectancy, health status, and prior screening history; and 3) clinicians discourage individuals older than 85 years from continuing CRC screening. The options for CRC screening are: fecal immunochemical test annually; high-sensitivity, guaiac-based fecal occult blood test annually; multitarget stool DNA test every 3 years; colonoscopy every 10 years; computed tomography colonography every 5 years; and flexible sigmoidoscopy every 5 years. CA Cancer J Clin 2018;68:250-281. © 2018 American Cancer Society.

An in vitro medium for modeling gut dysbiosis associated with cystic fibrosis.

The gut physiology of pediatric and adult persons with cystic fibrosis (pwCF) is altered relative to healthy persons. The CF gut is characterized, in part, as having excess mucus, increased fat content, acidic pH, increased inflammation, increased antibiotic perturbation, and the potential for increased oxygen availability. These physiological differences shift nutritional availability and the local environment for intestinal microbes, thus likely driving significant changes in microbial metabolism, colonization, and competition with other microbes. The impact of any specific change in this physiological landscape is difficult to parse using human or animal studies. Thus, we have developed a novel culture medium representative of the CF gut environment, inclusive of all the aforementioned features. This medium, called CF-MiPro, maintains CF gut microbiome communities, while significantly shifting nonCF gut microbiome communities toward a CF-like microbial profile, characterized by low Bacteroidetes and high Proteobacteria abundance. This medium is able to maintain this culture composition for up to 5 days of passage. Additionally, microbial communities passaged in CF-MiPro produce significantly less immunomodulatory short-chain fatty acids (SCFA), including propionate and butyrate, than communities passaged in MiPro, a culture medium representative of healthy gut physiology, confirming not only a shift in microbial composition but also altered community function. Our results support the potential for this in vitro culture medium as a new tool for the study of CF gut dysbiosis. IMPORTANCE Cystic fibrosis is an autosomal recessive disease that disrupts ion transport at mucosal surfaces, leading to mucus accumulation and altered physiology of both the lungs and the intestines, among other organs, with the resulting altered environment contributing to an imbalance of microbial communities. Culture media representative of the CF airway have been developed and validated; however, no such medium exists for modeling the CF intestine. Here, we develop and validate a first-generation culture medium inclusive of features that are altered in the CF colon. Our findings suggest this novel medium, called CF-MiPro, as a maintenance medium for CF gut microbiome samples and a flexible tool for studying key drivers of CF-associated gut dysbiosis.

Longitudinal adherence to annual colorectal cancer screening among Black persons living in the United States enrolled in a community-based randomized trial.

BACKGROUND: This study examined repeat colorectal cancer screening rates at 12 and 24 months as part of a randomized intervention trial among Black persons living in the United States and factors associated with screening adherence. METHODS: Participants completed a survey assessing demographics and Preventive Health Model (PHM) factors (e.g., self efficacy, susceptibility) and received either a culturally targeted photonovella plus free fecal immunochemical test (FIT) kits (intervention group) or a standard educational brochure plus free FIT kits (comparison group). FIT return was assessed at 6, 12, and 24 months. Descriptive statistics summarized patterns of repeat screening. Logistic regression models assessed FIT uptake overtime, and demographic and PHM factors associated with screening adherence. RESULTS: Participants (N = 330) were U.S.-born (93%), non-Hispanic (97%), and male (52%). Initial FIT uptake within 6 months of enrollment was 86.6%, and subsequently dropped to 54.5% at 12 months and 36.6% at 24 months. Higher FIT return rates were observed for the brochure group at 24 months (51.5% vs 33.3% photonovella, p = .023). Multiple patterns of FIT kit return were observed: 37% completed FIT at all three time points (full adherence), 22% completed two of three (partial adherence), 29% completed one of three (partial adherence), and 12% did not return any FIT kits (complete nonadherence). Predictors of full adherence were higher levels of education and self-efficacy. CONCLUSIONS: Full adherence to repeat screening was suboptimal. Most participants had partial adherence (one or two of three) to annual FIT screening. Future studies should focus on strategies to support repeat FIT screening.

Exploring the clinical significance of miR-148 expression variations in distinct subtypes of irritable bowel syndrome.

Irritable bowel syndrome (IBS) belongs to chronic functional gastrointestinal diseases featured by abdominal pain and changes in bowel habits. This study aimed to investigate the clinical significance of serum miR-148 expression in different subtypes of IBS. We enrolled 86 IBS patients and 55 healthy controls. miR-148 expression levels were assessed in IBS patients classified into IBS-constipation (IBS-C), IBS-diarrhea (IBS-D), and IBS-mixed stool pattern (IBS-M) subtypes. Receiver-operating characteristic (ROC) curves were employed to evaluate the diagnostic potential of miR-148 in distinguishing among IBS subtypes. Additionally, we analyzed the correlation between miR-148 expression and clinical characteristics, including IBS symptom severity. miR-148 expression was highest in IBS-D (diarrhea) group, followed by IBS-M and IBS-C. With the exception of the IBS-C group, miR-148 expression was elevated in IBS patients compared to controls. ROC curve analysis demonstrated that serum miR-148 exhibited higher diagnostic accuracy for discriminating IBS-C and IBS-D than IBS-M. Correlation analysis revealed a positive relationship between serum miR-148 relative expression and IBS symptom severity system scores. Univariate logistic analysis indicated a positive association between miR-148 expression and IBS-D and a negative correlation with IBS-C. miR-148 expression exhibits differential patterns among IBS subtypes and holds a potential to distinguish IBS-C and IBS-D. Furthermore, miR-148 expression correlates with the severity of IBS symptoms.

A Fecal MicroRNA Signature by Small RNA Sequencing Accurately Distinguishes Colorectal Cancers: Results From a Multicenter Study.

BACKGROUND & AIMS: Fecal tests currently used for colorectal cancer (CRC) screening show limited accuracy in detecting early tumors or precancerous lesions. In this respect, we comprehensively evaluated stool microRNA (miRNA) profiles as biomarkers for noninvasive CRC diagnosis. METHODS: A total of 1273 small RNA sequencing experiments were performed in multiple biospecimens. In a cross-sectional study, miRNA profiles were investigated in fecal samples from an Italian and a Czech cohort (155 CRCs, 87 adenomas, 96 other intestinal diseases, 141 colonoscopy-negative controls). A predictive miRNA signature for cancer detection was defined by a machine learning strategy and tested in additional fecal samples from 141 CRC patients and 80 healthy volunteers. miRNA profiles were compared with those of 132 tumors/adenomas paired with adjacent mucosa, 210 plasma extracellular vesicle samples, and 185 fecal immunochemical test leftover samples. RESULTS: Twenty-five miRNAs showed altered levels in the stool of CRC patients in both cohorts (adjusted P < .05). A 5-miRNA signature, including miR-149-3p, miR-607-5p, miR-1246, miR-4488, and miR-6777-5p, distinguished patients from control individuals (area under the curve [AUC], 0.86; 95% confidence interval [CI], 0.79-0.94) and was validated in an independent cohort (AUC, 0.96; 95% CI, 0.92-1.00). The signature classified control individuals from patients with low-/high-stage tumors and advanced adenomas (AUC, 0.82; 95% CI, 0.71-0.97). Tissue miRNA profiles mirrored those of stool samples, and fecal profiles of different gastrointestinal diseases highlighted miRNAs specifically dysregulated in CRC. miRNA profiles in fecal immunochemical test leftover samples showed good correlation with those of stool collected in preservative buffer, and their alterations could be detected in adenoma or CRC patients. CONCLUSIONS: Our comprehensive fecal miRNome analysis identified a signature accurately discriminating cancer aimed at improving noninvasive diagnosis and screening strategies.

Testing for Helicobacter pylori in an era of antimicrobial resistance.

Antimicrobial resistance in Helicobacter pylori has reached alarming levels and is compromising traditional empiric treatment of H. pylori. Antimicrobial susceptibility testing is routinely performed for infectious diseases when there is a risk of resistance and is now recommended to guide therapy for H. pylori. This mini-review overviews the current diagnostics for H. pylori with a focus on tests that enable susceptibility-guided treatment, including molecular tests performed directly on stool and endoscopically collected specimens.

Optimizing tracking and completion of follow-up colonoscopy after abnormal stool tests at health systems participating in the Centers for Disease Control and Prevention's Colorectal Cancer Control Program.

PURPOSE: We present findings from an assessment of award recipients' partners from the Centers for Disease Control and Prevention's Colorectal Cancer Control Program (CRCCP). We describe partners' processes of identifying and tracking patients undergoing stool-based screening. METHODS: We analyzed data from eight CRCCP award recipients purposively sampled and their partner health systems from 2019 to 2023. The data included number of stool-based tests distributed and returned; abnormal findings; referrals and completion of follow-up colonoscopies; and colonoscopy findings. We also report on strategies to improve tracking of stool-based tests and facilitation of follow-up colonoscopies. RESULTS: Five of eight CRCCP award recipients reported that all or some partner health systems were able to report stool test return rates. Six had health systems that were able to report abnormal stool test findings. Two reported that health systems could track time to follow-up colonoscopy completion from date of referral, while four could report colonoscopy completion but not the timeframe. Follow-up colonoscopy completion varied substantially from 24.2 to 75.5% (average of 47.9%). Strategies to improve identifying and tracking screening focused mainly on the use of electronic medical records; strategies to facilitate follow-up colonoscopy were multi-level. CONCLUSION: Health systems vary in their ability to track steps in the stool-based screening process and few health systems can track time to completion of follow-up colonoscopy. Longer time intervals can result in more advanced disease. CRCCP-associated health systems participating in this study could support the implementation of multicomponent strategies at the individual, provider, and health system levels to improve tracking and completion of follow-up colonoscopy.

Presence of SARS-CoV-2 RNA in COVID-19 survivors with post-COVID symptoms 2 years after hospitalization: The VIPER study.

The SARS-CoV-2 VIrus PERsistence (VIPER) study investigated the presence of long-lasting SARS-CoV-2 RNA in plasma, stool, urine, and nasopharyngeal samples in COVID-19 survivors. The presence of SARS-CoV-2 RNA reverse transcription polymerase chain reactions (RT-PCR) were analyzed within plasma, stool, urine, and nasopharyngeal swab samples in COVID-19 survivors with post-COVID symptoms and a comparison group of COVID-19 survivors without post-COVID symptoms matched by age, sex, body mass index and vaccination status. Participants self-reported the presence of any post-COVID symptom (defined as a symptom that started no later than 3 months after the initial infection). Fifty-seven (57.9% women, age: 51.1, standard deviation [SD]: 10.4 years) previously hospitalized COVID-19 survivors with post-COVID symptoms and 55 (56.4% women, age: 50.0, SD: 12.8 years) matched individuals who had a past SARS-CoV-2 infection without post-COVID symptoms were evaluated 27 (SD 7.5) and 26 (SD 8.7) months after hospital discharge, respectively. The presence of SARS-CoV-2 RNA was identified in three nasopharyngeal samples of patients with post-COVID symptoms (5.2%) but not in plasma, stool, or urine samples. Thus, SARS-CoV-2 RNA was not identified in any sample of survivors without post-COVID symptoms. The most prevalent post-COVID symptoms consisted of fatigue (93%), dyspnea, and pain (both, 87.7%). This study did not find SARS-CoV-2 RNA in plasma, stool, or urine samples, 2 years after the infection. A prevalence of 5.2% of SARS-CoV-2 RNA in nasopharyngeal samples, suggesting a potential active or recent reinfection, was found in patients with post-COVID symptoms. These results do not support the association between SARS-CoV-2 RNA in plasma, stool, urine, or nasopharyngeal swab samples and post-COVID symptomatology in the recruited population.

Stool and blood metabolomics in the metabolic syndrome: a cross-sectional study.

INTRODUCTION/OBJECTIVES: Changes in the stool metabolome have been poorly studied in the metabolic syndrome (MetS). Moreover, few studies have explored the relationship of stool metabolites with circulating metabolites. Here, we investigated the associations between stool and blood metabolites, the MetS and systemic inflammation. METHODS: We analyzed data from 1,370 participants of the KORA FF4 study (Germany). Metabolites were measured by Metabolon, Inc. (untargeted) in stool, and using the AbsoluteIDQ® p180 kit (targeted) in blood. Multiple linear regression models, adjusted for dietary pattern, age, sex, physical activity, smoking status and alcohol intake, were used to estimate the associations of metabolites with the MetS, its components and high-sensitivity C-reactive protein (hsCRP) levels. Partial correlation and Multi-Omics Factor Analysis (MOFA) were used to investigate the relationship between stool and blood metabolites. RESULTS: The MetS was significantly associated with 170 stool and 82 blood metabolites. The MetS components with the highest number of associations were triglyceride levels (stool) and HDL levels (blood). Additionally, 107 and 27 MetS-associated metabolites (in stool and blood, respectively) showed significant associations with hsCRP levels. We found low partial correlation coefficients between stool and blood metabolites. MOFA did not detect shared variation across the two datasets. CONCLUSIONS: The MetS, particularly dyslipidemia, is associated with multiple stool and blood metabolites that are also associated with systemic inflammation. Further studies are necessary to validate our findings and to characterize metabolic alterations in the MetS. Although our analyses point to weak correlations between stool and blood metabolites, additional studies using integrative approaches are warranted.

A multi-cohort phase 1b trial of rituximab in combination with immunotherapy doublets in relapsed/refractory follicular lymphoma.

Antibodies targeting PD-1 or 4-1BB achieve objective responses in follicular lymphoma (FL), but only in a minority of patients. We hypothesized that targeting multiple immune receptors could overcome immune resistance and increase response rates in patients with relapsed/refractory FL. We therefore conducted a phase 1b trial testing time-limited therapy with different immunotherapy doublets targeting 4-1BB (utomilumab), OX-40 (ivuxolimab), and PD-L1 (avelumab) in combination with rituximab among patients with relapsed/refractory grade 1-3A FL. Patients were enrolled onto 2 of 3 planned cohorts (cohort 1 - rituximab/utomilumab/avelumab; cohort 2 - rituximab/ivuxolimab/utomilumab). 3+3 dose escalation was followed by dose expansion at the recommended phase 2 dose (RP2D). Twenty-four patients were enrolled (16 in cohort 1 and 9 in cohort 2, with one treated in both cohorts). No patients discontinued treatment due to adverse events and the RP2D was the highest dose level tested in both cohorts. In cohort 1, the objective and complete response rates were 44% and 19%, respectively (50% and 30%, respectively, at RP2D). In cohort 2, no responses were observed. The median progression-free survivals in cohorts 1 and 2 were 6.9 and 3.2 months, respectively. In cohort 1, higher density of PD-1+ tumor-infiltrating T-cells on baseline biopsies and lower density of 4-1BB+ and TIGIT+ T-cells in on-treatment biopsies were associated with response. Abundance of Akkermansia in stool samples was also associated with response. Our results support a possible role for 4-1BB agonist therapy in FL and suggest that features of the tumor microenvironment and stool microbiome may be associated with clinical outcomes (NCT03636503).

Fecal miRNA profiles in colorectal cancers with mucinous morphology.

Diagnostic performance of molecular markers in surrogate tissues like stool may be affected by colorectal cancer (CRC) morphological heterogeneity. The mucinous histotype represents a subgroup of CRC with a peculiar molecular program and unfavorable disease progression. However, the percentage of mucinous morphology necessary to define this subtype is still a matter of debate. In this study, we investigated whether stool miRNA profiles of CRC patients differ in patients with mucinous histopathological subtypes compared to non-mucinous cancers. In this respect, we also explored how the stool miRNA signature reported in our previous multicentric study (Pardini et al., Gastroenterology 2023) behave in this histotype. Small-RNA sequencing was performed in fecal and tissue samples of an Italian cohort (n=172), including 27 CRC with mucinous morphology (mucinous cancers with >50% mucinous morphology and those with mucinous component >5% but <50%), 58 non-mucinous CRC, and 87 colonoscopy-negative controls. Results were compared with fecal miRNA profiles of a cohort from the Czech Republic (n=98). Most of the differentially expressed (DE) stool miRNAs (n=324) were in common between CRC with mucinous morphology and non-mucinous histopathological subtypes in comparison with healthy controls. Interestingly, the altered levels of 25 fecal miRNAs previously identified distinguishing CRC cases from controls in both cohorts were also confirmed after stratification for mucinous morphology. Forty-nine miRNAs were DE exclusively in CRC with mucinous morphology and 61 in non-mucinous CRC. Mucinous cancers and those with mucinous component showed fairly similar profiles that were comparable in the Czech cohort. Among the stool DE miRNAs observed in CRC with mucinous morphology, 20 were also altered in the comparison between tumor and adjacent mucosa tissue. This study highlights miRNAs specifically altered in CRC with mucinous morphology. Nevertheless, the performance of our stool miRNA signature in accurately distinguishing CRC cases from controls was not significantly affected by this histological subtype. This aspect further supports the use of stool miRNAs for noninvasive diagnosis and screening strategies.

Validation of collection and anaerobic fermentation techniques for measuring prebiotic impact on gut microbiota.

BACKGROUND: Defining the ability of prebiotic dietary carbohydrates to influence the composition and metabolism of the gut microbiota is central to defining their health impact in diverse individuals. Many clinical trials are using indirect methods. This study aimed to validate collection and fermentation methods enabling their use in the context of clinical studies. METHODS AND RESULTS: Parameters tested included stool sample acquisition, storage, and growth conditions. Stool from 3 infants and 3 adults was collected and stored under varying conditions. Samples were cultured anaerobically for two days in the presence of prebiotics, whereupon optical density and pH were measured across time. Whole genome shotgun sequencing and NMR metabolomics were performed. Neither the type of collection vial (standard vial and two different BD anaerobic collection vials) nor cryopreservation (-80 °C or 4 °C) significantly influenced either microbial composition at 16 h of anaerobic culture or the principal components of the metabolome at 8 or 16 h. Metagenomic differences were driven primarily by subject, while metabolomic differences were driven by fermentation sugar (2'-fucosyllactose or dextrose). CONCLUSIONS: These data identified a feasible and valid approach for prebiotic fermentation analysis of individual samples in large clinical studies: collection of stool microbiota using standard vials; cryopreservation prior to testing; and collecting fermentation read-out at 8 and 16 hr. Thus, fermentation analysis can be a valid technique for testing the effects of prebiotics on human fecal microbiota.

Predictors of stool deoxyribonucleic acid test use in the United States: Implications for outreach to under-resourced populations.

OBJECTIVE: Although colorectal cancer screening (CRCS) is a public health priority, uptake is suboptimal in under-resourced groups. Noninvasive modalities, including stool deoxyribonucleic acid (sDNA) testing, may mitigate economic, geographic, cultural, or impairment-related barriers to CRCS. We assessed use of sDNA testing and other CRCS modalities in U.S. residents, comparing subgroups defined by several social determinants of health (SDOH). METHODS: A nationally representative sample of community-dwelling respondents aged 50-75 years self-reported use of CRCS modalities in the 2020 Behavioral Risk Factor Surveillance System Survey. Statistical analyses assessed up-to-date screening status and choice of modality in the recommended screening interval. RESULTS: Of 179,833 sampled respondents, 60.8% reported colonoscopy, 5.7% sDNA testing, 5.5% another modality. The rate of up-to-date screening was 72.0% overall and negatively associated with Hispanic ethnicity (63.6%), lower educational and annual income levels (e.g.,

Association between dietary inflammatory index and energy-adjusted dietary inflammatory index and constipation in US adults.

BACKGROUND: Diet and inflammation are associated with constipation. Dietary inflammation index (DII) and energy-dietary inflammation index (E-DII) have not been evaluated together with constipation. Therefore, this study was conducted to further observe the relationship between DII and E-DII and constipation in American adults. METHODS: Data were extracted from the National Health and Nutrition Examination Survey (NHANES) for 12,400 adults aged 20 years and older between 2005 and 2010. DII and E-DII were obtained by employing data from the two 24-h dietary recall of the participants. Constipation was defined and categorized using the Bristol Stool Form Scale. RESULTS: In the logistic regression model, the relationship between DII and E-DII and constipation remained positive after adjusting for confounding factors (odds ratio [OR] = 1.13; 95% confidence interval [CI]: 1.07-1.20 in DII logistic regression model III; odds ratio [OR] = 1.09; 95% confidence interval [CI]: 1.03-1.17 in E-DII logistic regression model III). Constipation was more common in quartile 4 (DII: 2.87-5.09; E-DII: 1.78-8.95) than in quartile 1 (DII: -5.11-0.25; E-DII: -2.60-0.11) (OR = 1.79, 95% CI: 1.30-2.47 in DII and OR = 1.75, 95% CI: 1.25-2.46 in E-DII for all participants; OR = 2.04, 95% CI: 1.39-3.00 in DII OR = 2.20, 95% CI: 1.39-3.47 in E-DII for males; OR = 1.86, 95% CI: 1.08-3.22 and OR = 1.80, 95% CI: 1.06-3.06 for females). These results were confirmed using multiple imputations. CONCLUSIONS: The findings of this study show that a high DII and E-DII were associated with an increased incidence of constipation among US adults.

A stool based qPCR for the diagnosis of TB in children and people living with HIV in Uganda, Eswatini and Mozambique (Stool4TB): a protocol for a multicenter diagnostic evaluation.

BACKGROUND: Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples. Thus, novel diagnostic strategies, based on non-respiratory specimens could improve clinical decision making and TB outcomes in high burden TB settings. We propose a multi-country, prospective diagnostic evaluation study with a nested longitudinal cohort evaluation to assess the performance of a new stool-based qPCR, developed by researchers at Baylor College of Medicine (Houston, Texas, USA) for TB bacteriological confirmation with promising results in pilot studies. METHODS: The study will take place in high TB/HIV burden countries (Mozambique, Eswatini and Uganda) where we will enroll, over a period of 30 months, 650 PLHIV (> 15) and 1295 children under 8 years of age (irrespective of HIV status) presenting pressumptive TB. At baseline, all participants will provide clinical history, complete a physical assessment, and undergo thoracic chest X-ray imaging. To obtain bacteriological confirmation, participants will provide respiratory samples (1 for adults, 2 in children) and 1 stool sample for Xpert Ultra MTB/RIF (Cepheid, Sunnyvale, CA, USA). Mycobacterium tuberculosis (M.tb) liquid culture will only be performed in respiratory samples and lateral flow lipoarabinomannan (LF-LAM) in urine following WHO recommendations. Participants will complete 2 months follow-up if they are not diagnosed with TB, and 6 months if they are. For analytical purposes, the participants in the pediatric cohort will be classified into "confirmed tuberculosis", "unconfirmed tuberculosis" and "unlikely tuberculosis". Participants of the adult cohort will be classified as "bacteriologically confirmed TB", "clinically diagnosed TB" or "not TB". We will assess accuracy of the novel qPCR test compared to bacteriological confirmation and Tb diagnosis irrespective of laboratory results. Longitudinal qPCR results will be analyzed to assess its use as treatment response monitoring. DISCUSSION: The proposed stool-based qPCR is an innovation because both the strategy of using a non-sputum based sample and a technique specially designed to detect M.tb DNA in stool. PROTOCOL REGISTRATION DETAILS: ClinicalTrials.gov Identifier: NCT05047315.

Monitoring the VDPV2 outbreak in Egypt during 2020-2021 highlights the crucial role of environmental surveillance and boosting immunization in combating Poliovirus.

BACKGROUND: Poliovirus is a highly infectious enterovirus (EV) that primarily affects children and can lead to lifelong paralysis or even death. Vaccine-derived polioviruses (VDPVs) are a great threat since they are derived from the attenuated virus in the Oral Poliovirus Vaccine (OPV) and can mutate to a more virulent form. The purpose of this study was to identify VDPV serotype 2 through the year 2020-2021 via surveillance of sewage samples collected from different localities and governorates in Egypt and stool specimens from Acute Flaccid Paralysis (AFP) cases. Both were collected through the national poliovirus surveillance system and according to the guidelines recommended by the WHO. METHODS: A total of 1266 sewage samples and 3241 stool samples from January 2020 to December 2021 were investigated in the lab according to World Health Organization (WHO) protocol for the presence of Polioviruses by cell culture, molecular identification of positive isolates on L20B cell line was carried out using real-time polymerase chain reactions (RT-PCR). Any positive isolates for Poliovirus type 2 and isolates suspected of Vaccine Derived Poliovirus Type 1 and type 3 screened by (VDPV1) or Vaccine Poliovirus Type 3 (VDPV3) assay in RT-PCR were referred for VP1 genetic sequencing. RESULTS: The outbreak was caused by circulating VDPV2 (cVDPV2) strains started in January 2021. By the end of February 2021, a total of 11 cVDPV2s were detected in sewage samples from six governorates confirming the outbreak situation. One additional cVDPV2 was detected later in the sewage sample from Qena (June 2021). The first and only re-emergence of VDPV2 in stool samples during the outbreak was in contact with Luxor in June 2021. By November 2021, a total of 80 VDPVs were detected. The Egyptian Ministry of Health and Population (MOHP), in collaboration with the WHO, responded quickly by launching two massive vaccination campaigns targeting children under the age of five. Additionally, surveillance systems were strengthened to detect new cases and prevent further spread of the virus. CONCLUSION: The continued threat of poliovirus and VDPVs requires ongoing efforts to prevent their emergence and spread. Strategies such as improving immunization coverage, using genetically stable vaccines, and establishing surveillance systems are critical to achieving global eradication of poliovirus and efficient monitoring of VDPVs outbreaks.

Acacia fiber or probiotic supplements to relieve gastrointestinal complaints in patients with constipation-predominant IBS: a 4-week randomized double-blinded placebo-controlled intervention trial.

PURPOSE: To date, no adequate treatment for irritable bowel syndrome with predominant constipation complaints (IBS-C) is available. Fibers with prebiotic properties and probiotic compounds have shown promise in relieving IBS-C-related complaints. We aimed to determine the effects of a 4-week intervention with either an Acacia fiber (AF) with prebiotic properties or a probiotic Bifidobacterium Lactis (BLa80) supplement, compared to a control supplement, on stool pattern, IBS symptoms and Quality of Life (QoL), in IBS-C individuals. METHODS: A parallel, double-blind, randomized controlled trial involving 180 subjects meeting the ROME IV criteria for IBS-C was conducted. Following a 4-week observation period, subjects received either AF (10 g), Probiotic BLa80 (4 g; 2 × 1011 CFU/g) or a maltodextrin placebo (10 g) daily for 4 weeks. Subjects reported daily information on stool pattern and gastrointestinal complaints. Before and after each 4-week period, questionnaires on symptom severity, constipation symptoms, anxiety and depression and QoL were completed. Stool mass was measured for 5-days before and after the intervention. RESULTS: Stool frequency significantly improved in the AF and Probiotic BLa80 groups compared to placebo (P < 0.001, P = 0.02, respectively). Probiotic BLa80 showed a significant reduction in IBS symptom severity (P = 0.03), for AF a trend towards decreased constipation symptoms (PAC-SYM, P = 0.10) was observed. No significant changes in stool consistency, stool mass or QoL measures were observed between the AF and Probiotic BLa80 compared to placebo. CONCLUSION: Daily dietary supplementation with Acacia fiber and probiotic supplements might help IBS-C patients by relieving IBS-related complaints compared to a placebo supplement. REGISTRATION NUMBER OF CLINICAL TRIAL: The trial is registered at ClinicalTrials.gov: NCT04798417: Study Details | Nutrition to Relieve IBS Constipation | ClinicalTrials.gov.

Unveiling the applicability of the Brussels Infant and Toddler Stool Scale for hard stool in young children: A South Asian perspective.

BACKGROUND AND AIM: The Rome IV criteria, the standard for diagnosing functional constipation (FC), deem the Bristol Stool Scale (BSS) unsuitable for assessing stool consistency in young children. Hence, the Brussels Infant and Toddler Stool Scale (BITSS) was developed. We aimed to validate and test the reliability of BITSS for hard stools and FC among infants and toddlers, where there is limited evidence in Asian populations. METHODS: The research evaluated FC in children aged 0-48 months who came for medical examination using Rome IV criteria. Stool properties provided by caregivers were assessed sequentially through three methods: the BSS, the BITSS, and caregiver reports. RESULTS: A total of 370 responses were received, with an average age of 26.2 months. Substantial agreement was observed between the BITSS and caregiver reports for hard stools (concordance rate: 91.9%, κ = 0.75), while near-perfect agreement was found between BITSS and BSS (concordance rate: 93.5%, κ = 0.81). The BITSS exhibited higher sensitivity than the BSS in assessing hard stools (95.3% vs 87.5%, P < 0.001). And the BITSS (23.5%) identified the highest prevalence of FC than the BSS (20.5%) and caregiver report (18.7%), with near-perfect agreement. Moderate agreement was reported when evaluating the test-retest reliability between BITSS and caregiver reports (concordance rate: 86.2%, κ = 0.44). CONCLUSIONS: The BITSS, more sensitive than the BSS in identifying abnormal, especially hard stools, aids in early FC detection in young children. These findings support using BITSS over BSS for evaluating hard stools in infants and toddlers, both in Vietnam and globally.

Home-based fecal calprotectin utilization in a general pediatric gastroenterology clinic.

OBJECTIVE: Remote investigation and monitoring have gained importance in ambulatory practice. A home-based fecal calprotectin (FC) test has been developed where the sample is processed and analyzed at home through a smartphone application. We aimed to assess the use of standard ELISA (sFC) versus home-based (hFC) FC testing in a general pediatric gastroenterology clinic. METHODS: Ambulatory pediatric patients with hFC or sFC performed between August 2019 and November 2020 were included. Data regarding demographics, clinical characteristics, medication use, investigations, and final diagnosis, categorized as inflammatory bowel disease (IBD), functional gastrointestinal (GI) disorders, organic non-IBD (ONI) GI disorders, non-GI disorders, and undetermined after 6 months of investigation, were recorded. RESULTS: A total of 453 FC tests from 453 unique patients were included. Of those, 249 (55%) were hFC. FC levels (median) were higher in children with IBD compared to non-IBD diagnosis (sFC 795 vs. 57 µg/g, hFC 595 vs. 47 µg/g, p < 0.001), and in ONI compared to functional GI disorders (sFC 85 vs. 54 µg/g, p = 0.003, hFC 57 vs. 40 µg/g, p < 0.001). No significant difference was observed between different ONI GI disorders or subtypes of functional disorders. Age did not significantly influence levels. CONCLUSIONS: Overall, hFC and sFC provide similar results in the general pediatric GI ambulatory setting. FC is a sensitive but not disease-specific marker to identify patients with IBD. Values appear to be higher in ONI GI disorders over functional disorders, although cut-off values have yet to be determined.