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IMeta Jun 2024() is the predominant causative agent of nosocomial diarrhea worldwide. Infection with occurs due to the secretion of large glycosylating toxin proteins, which can... (Review)
Review
() is the predominant causative agent of nosocomial diarrhea worldwide. Infection with occurs due to the secretion of large glycosylating toxin proteins, which can lead to toxic megacolon or mortality in susceptible hosts. A critical aspect of biology is its ability to persist asymptomatically within the human host. Individuals harboring asymptomatic colonization or experiencing a single episode of infection (CDI) without recurrence exhibit heightened immune responses compared to symptomatic counterparts. The significance of these immune responses cannot be overstated, as they play critical roles in the development, progression, prognosis, and outcomes of CDI. Nonetheless, our current comprehension of the immune responses implicated in CDI remains limited. Therefore, further investigation is imperative to elucidate their underlying mechanisms. This review explores recent advancements in comprehending CDI pathogenesis and how the host immune system response influences disease progression and severity, aiming to enhance our capacity to develop immunotherapy-based treatments for CDI.
PubMed: 38898983
DOI: 10.1002/imt2.200 -
Langenbeck's Archives of Surgery Jun 2024Coloanal anastomosis with loop diverting ileostomy (CAA) is an option for low anterior resection of the rectum, and Turnbull-Cutait coloanal anastomosis (TCA) regained... (Meta-Analysis)
Meta-Analysis Comparative Study
Turnbull-Cutait pull-through coloanal anastomosis versus standard coloanal anastomosis plus diverting ileostomy for low anterior resection: a meta-analysis and systematic review.
PURPOSE
Coloanal anastomosis with loop diverting ileostomy (CAA) is an option for low anterior resection of the rectum, and Turnbull-Cutait coloanal anastomosis (TCA) regained popularity in the effort to offer patients a reconstructive option. In this context, we aimed to compare both techniques.
METHODS
PubMed, Cochrane, and Scopus were searched for studies published until January 2024. Odds ratios (RRs) with 95% confidence intervals (CIs) were pooled with a random-effects model. Statistical significance was defined as p < 0.05. Heterogeneity was assessed using the Cochran Q test and I statistics, with p-values inferior to 0.10 and I >25% considered significant. Statistical analysis was conducted in RStudio version 4.1.2 (R Foundation for Statistical Computing). Registered number CRD42024509963.
RESULTS
One randomized controlled trial and nine observational studies were included, comprising 1,743 patients, of whom 899 (51.5%) were submitted to TCA and 844 (48.5%) to CAA. Most patients had rectal cancer (52.2%), followed by megacolon secondary to Chagas disease (32.5%). TCA was associated with increased colon ischemia (OR 3.54; 95% CI 1.13 to 11.14; p < 0.031; I = 0%). There were no differences in postoperative complications classified as Clavien-Dindo ≥ IIIb, anastomotic leak, pelvic abscess, intestinal obstruction, bleeding, permanent stoma, or anastomotic stricture. In subgroup analysis of patients with cancer, TCA was associated with a reduction in anastomotic leak (OR 0.55; 95% CI 0.31 to 0.97 p = 0.04; I = 34%).
CONCLUSION
TCA was associated with a decrease in anastomotic leak rate in subgroups analysis of patients with cancer.
Topics: Humans; Anastomosis, Surgical; Ileostomy; Rectal Neoplasms; Colon; Anal Canal; Proctectomy; Anastomotic Leak; Postoperative Complications
PubMed: 38888662
DOI: 10.1007/s00423-024-03379-9 -
Journal of Visualized Experiments : JoVE May 2024Ulcerative colitis (UC) is a chronic immune-mediated disease that affects the entire colon and rectum with a relapsing and remitting course, causing lifelong morbidity....
Ulcerative colitis (UC) is a chronic immune-mediated disease that affects the entire colon and rectum with a relapsing and remitting course, causing lifelong morbidity. When medical treatment is ineffective, especially in cases of massive gastrointestinal bleeding, perforation, toxic megacolon, or carcinogenesis, surgery becomes the last line of defense to cure UC. Total colorectal resection and ileal pouch-anal anastomosis (IPAA) offer the best chance for long-term treatment. Pouchitis is the most common and troublesome postoperative complication. In this investigation, microsurgery is employed to create an ileal pouch model in experimental rats via IPAA surgery. Subsequently, a sustained rat model of pouchitis is established by inducing inflammation of the ileal pouch with dextran sulfate sodium (DSS). The successful establishment of rat pouchitis is validated through analysis of postoperative general status, weight, food and water intake, fecal data, as well as pouch tissue pathology, immunohistochemistry, and inflammatory factor analysis. This experimental animal model of pouchitis provides a foundation for studying the pathogenesis and treatment of the condition.
Topics: Animals; Pouchitis; Rats; Disease Models, Animal; Proctocolectomy, Restorative; Dextran Sulfate; Colonic Pouches; Postoperative Complications; Male; Anastomosis, Surgical
PubMed: 38884498
DOI: 10.3791/66623 -
Journal of Surgical Case Reports Jun 2024Toxic megacolon denotes an abrupt non-obstructive distension of the colon, accompanied by systemic signs of toxicity. Mortality rates can soar as high as 7.9%. While...
Toxic megacolon denotes an abrupt non-obstructive distension of the colon, accompanied by systemic signs of toxicity. Mortality rates can soar as high as 7.9%. While primarily linked with chronic bowel conditions, the incidence attributed to has surged due to the indiscriminate use of broad-spectrum antibiotics. Surgical intervention becomes necessary in the majority of cases. Herein, we illustrate the case of a 50-year-old female presenting with episodic epigastric pain lasting 9 h, vomiting, and watery bowel movements, devoid of peritoneal irritation findings and lacking a history of chronic intestinal inflammation. Under certain circumstances, toxic megacolon may manifest atypically, underscoring the importance of conducting a comprehensive medical history and clinical assessment. Moreover, it is imperative to solicit pertinent paraclinical investigations to address the patient holistically and foster a favorable clinical outcome.
PubMed: 38863961
DOI: 10.1093/jscr/rjae403 -
Scientific Reports Jun 2024Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.71A>G), the most common RMRP...
Cartilage-hair hypoplasia syndrome (CHH) is an autosomal recessive disorder frequently linked to n.72A>G (previously known as n.70A>G and n.71A>G), the most common RMRP variant worldwide. More than 130 pathogenic variants in this gene have already been described associated with CHH, and founder alterations were reported in the Finnish and Japanese populations. Our previous study in Brazilian CHH patients showed a high prevalence of n.197C>T variant (former n.195C>T and n.196C>T) when compared to other populations. The aim of this study was to investigate a possible founder effect of the n.197C>T variant in the RMRP gene in a series of CHH Brazilian patients. We have selected four TAG SNPs within chromosome 9 and genotyped the probands and their parents (23 patients previously described and nine novel). A common haplotype to the n.197C>T variant carriers was identified. Patients were also characterized for 46 autosomal Ancestry Informative Markers (AIMs). European ancestry was the most prevalent (58%), followed by African (24%) and Native American (18%). Our results strengthen the hypothesis of a founder effect for the n.197C>T variant in Brazil and indicate that this variant in the RMRP gene originated from a single event on chromosome 9 with a possible European origin.
Topics: Humans; Brazil; Founder Effect; Hirschsprung Disease; Male; Osteochondrodysplasias; Female; Polymorphism, Single Nucleotide; Hair; RNA, Long Noncoding; Haplotypes; Primary Immunodeficiency Diseases; Hypotrichosis; Chromosomes, Human, Pair 9; Child
PubMed: 38862721
DOI: 10.1038/s41598-024-64407-8 -
Infection & Chemotherapy May 2024Enterocolitis and gastroenteritis remain major health problems, particularly in children living in developing countries. Intestinal protozoa, such as , and are...
BACKGROUND
Enterocolitis and gastroenteritis remain major health problems, particularly in children living in developing countries. Intestinal protozoa, such as , and are frequently associated with these conditions. Amebic colitis can cause serious complications, including fulminant necrotizing colitis, toxic megacolon, extraintestinal amebiasis, and stunting in children. The diagnosis of amoebiasis is challenging, relying on microscopic examination, which cannot distinguish from the nonpathogenic and Therefore, this study aimed to identify intestinal parasites, particularly , their prevalence, and the clinical characteristics of patients admitted for enterocolitis and gastroenteritis at a tertiary-referral hospital.
MATERIAL AND METHODS
A cross-sectional, retrospective study was conducted at a national, tertiary-referral government hospital, in Jakarta. Of the 111 retrieved medical records from hospitalized patients with enterocolitis and gastroenteritis, 54 (48.6%) fecal samples were still available in the laboratory storage and referred to the parasitology laboratory. All fecal samples underwent the following tests: 1) direct stool examination, after staining with 1% Lugol's solution, and using the water-ether concentration method; 2) modified acid-fast staining for coccidian parasites; 3) Jones' culture medium to detect ; 4) copro-antigen assay to detect and and 5) a polymerase chain reaction (PCR) assay to identify . Clinical and demographic data were obtained from the medical records.
RESULTS
Largely, patients (44.1%) were from the cohort of young children ≤5 years old, followed by adults aged 19-60 years old (24.3%). Both cohorts exhibited polyparasitism. Intestinal parasites were detected in 17 out of the 54 samples (31.4%). These included 6 (11.1%), 2 (3.7%),5 (9.2%), 3 (5.5%), 2 (3.7%), and 1 (1.8%) samples that were positive for , , , , and respectively. PCR analysis revealed that 10 samples were positive for infection, eight of which originated from pediatric patients.
CONCLUSION
At a national tertiary-referral hospital in Indonesia, infection was most prevalent among pediatric patients with enterocolitis. and were the two main species identified by PCR. Therefore, PCR assays and fecal occult-blood tests are recommended in cases of enterocolitis and gastroenteritis.
PubMed: 38859717
DOI: 10.3947/ic.2023.0099 -
Orphanet Journal of Rare Diseases Jun 2024Waardenburg syndrome (WS) is a rare genetic disorder mainly characterized by hearing loss and pigmentary abnormalities. Currently, seven causative genes have been...
BACKGROUND
Waardenburg syndrome (WS) is a rare genetic disorder mainly characterized by hearing loss and pigmentary abnormalities. Currently, seven causative genes have been identified for WS, but clinical genetic testing results show that 38.9% of WS patients remain molecularly unexplained. In this study, we performed multi-data integration analysis through protein-protein interaction and phenotype-similarity to comprehensively decipher the potential causative factors of undiagnosed WS. In addition, we explored the association between genotypes and phenotypes in WS with the manually collected 443 cases from published literature.
RESULTS
We predicted two possible WS pathogenic genes (KIT, CHD7) through multi-data integration analysis, which were further supported by gene expression profiles in single cells and phenotypes in gene knockout mouse. We also predicted twenty, seven, and five potential WS pathogenic variations in gene PAX3, MITF, and SOX10, respectively. Genotype-phenotype association analysis showed that white forelock and telecanthus were dominantly present in patients with PAX3 variants; skin freckles and premature graying of hair were more frequently observed in cases with MITF variants; while aganglionic megacolon and constipation occurred more often in those with SOX10 variants. Patients with variations of PAX3 and MITF were more likely to have synophrys and broad nasal root. Iris pigmentary abnormality was more common in patients with variations of PAX3 and SOX10. Moreover, we found that patients with variants of SOX10 had a higher risk of suffering from auditory system diseases and nervous system diseases, which were closely associated with the high expression abundance of SOX10 in ear tissues and brain tissues.
CONCLUSIONS
Our study provides new insights into the potential causative factors of WS and an alternative way to explore clinically undiagnosed cases, which will promote clinical diagnosis and genetic counseling. However, the two potential disease-causing genes (KIT, CHD7) and 32 potential pathogenic variants (PAX3: 20, MITF: 7, SOX10: 5) predicted by multi-data integration in this study are all computational predictions and need to be further verified through experiments in follow-up research.
Topics: Waardenburg Syndrome; Humans; Microphthalmia-Associated Transcription Factor; SOXE Transcription Factors; PAX3 Transcription Factor; Mice; Animals; Phenotype; Genotype; Mutation
PubMed: 38844942
DOI: 10.1186/s13023-024-03220-y -
The Brazilian Journal of Infectious... 2024C. difficile has been increasingly reported as a cause of gastrointestinal disease in children, ranging from mild self-limiting diarrhea to severe conditions such as...
Molecular epidemiology and antimicrobial resistance in Clostridioides difficile strains isolated from children and adolescents in a tertiary referral pediatric hospital in Fortaleza, Brazil.
BACKGROUND
C. difficile has been increasingly reported as a cause of gastrointestinal disease in children, ranging from mild self-limiting diarrhea to severe conditions such as pseudomembranous colitis and toxic megacolon. Only two pediatric research groups reported the presence of C. difficile infection in Brazilian children, but no previous research has examined C. difficile infection among children in northeastern Brazil. This prospective cross-sectional study investigated the molecular epidemiology and antimicrobial resistance of C. difficile strains isolated from children and adolescents with diarrhea referred to a tertiary pediatric hospital in Brazil while exploring the associated risk factors.
RESULTS
Toxin positivity or C. difficile isolation was found in 30.4 % (17/56) samples. C. difficile was isolated from 35 % (6/17) samples. Four toxigenic strains were identified (tpi+, tcdA+, tcdB+, cdtB-, without tcdC deletions) belonging to PCR ribotypes and PFGE-pulsotypes: 046 (new pulsotype 1174), 106 (NAP11), 002 (new pulsotype 1274), 012 (new pulsotype NML-1235). Two of the six isolates belonging to ribotypes 143 and 133 were non-toxigenic. All toxigenic strains were sensitive to metronidazole and vancomycin. Regarding the clinical manifestation, diarrhea lasted an average of 11 days, ranging from 3 to 50 days and was often associated with mucus and/or blood. All six patients from whom the C. difficile was isolated had a chronic disease diagnosis, with these comorbidities as the main risk factors.
CONCLUSION
Our study enhances our understanding of the present epidemiological landscape of C. difficile-associated diarrhea (CDI) among children in northeastern Brazil, reveling a substantial CDI frequency of 30.4 %, with toxigenic strains detected in 76.4 % of cases, highlighting a higher prevalence compared to earlier Brazilian studies. In the globalized world, an understanding of disease-generating strains, the associated risk factors, clinical manifestation, and antimicrobial sensitivity has fundamental epidemiological importance and draws attention to preventive measures, allowing for more decisive action.
Topics: Humans; Clostridioides difficile; Child; Adolescent; Female; Male; Brazil; Cross-Sectional Studies; Prospective Studies; Tertiary Care Centers; Child, Preschool; Anti-Bacterial Agents; Clostridium Infections; Microbial Sensitivity Tests; Risk Factors; Infant; Hospitals, Pediatric; Molecular Epidemiology; Diarrhea; Ribotyping; Drug Resistance, Bacterial
PubMed: 38843868
DOI: 10.1016/j.bjid.2024.103767 -
PloS One 2024The vertebrate enteric nervous system (ENS) is a crucial network of enteric neurons and glia resident within the entire gastrointestinal tract (GI). Overseeing essential...
The vertebrate enteric nervous system (ENS) is a crucial network of enteric neurons and glia resident within the entire gastrointestinal tract (GI). Overseeing essential GI functions such as gut motility and water balance, the ENS serves as a pivotal bidirectional link in the gut-brain axis. During early development, the ENS is primarily derived from enteric neural crest cells (ENCCs). Disruptions to ENCC development, as seen in conditions like Hirschsprung disease (HSCR), lead to the absence of ENS in the GI, particularly in the colon. In this study, using zebrafish, we devised an in vivo F0 CRISPR-based screen employing a robust, rapid pipeline integrating single-cell RNA sequencing, CRISPR reverse genetics, and high-content imaging. Our findings unveil various genes, including those encoding opioid receptors, as possible regulators of ENS establishment. In addition, we present evidence that suggests opioid receptor involvement in the neurochemical coding of the larval ENS. In summary, our work presents a novel, efficient CRISPR screen targeting ENS development, facilitating the discovery of previously unknown genes, and increasing knowledge of nervous system construction.
Topics: Animals; Enteric Nervous System; Zebrafish; CRISPR-Cas Systems; Zebrafish Proteins; Neural Crest; Hirschsprung Disease
PubMed: 38809858
DOI: 10.1371/journal.pone.0303914 -
Cureus Apr 2024infection (CDI) is a clinical and laboratory diagnosis. Populations at higher risk of developing disease require a high clinical index of suspicion for laboratory... (Review)
Review
INTRODUCTION
infection (CDI) is a clinical and laboratory diagnosis. Populations at higher risk of developing disease require a high clinical index of suspicion for laboratory testing to avoid incorrect assumptions of colonization. Common risk factors include recent antibiotic use, elderly (>65 years old), and immunocompromised patients. ssays should be ordered in an algorithm approach to diagnose an infection rather than colonization. Screening tests are widely available in hospital systems, but novel molecular testing may aid in diagnosis in patients with inconclusive or discordant antigen and toxin test results. Methods: Data was extracted from PubMed, Scopus, and Cumulative Index of Nursing and Allied Health Literature (CINAHL) databases based on the keywords "", "toxin assay", and "toxic megacolon". The data extracted is based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines. A total of 27 reports were included in this systematic review.
RESULTS
Testing patients with a significant gastrointestinal surgical history, hypogammaglobulinemia, inflammatory bowel disease, intensive care unit, and immunocompromised patients for CDI is highly recommended. Diarrhea in these subsets of patients requires correlation of clinical context and an understanding of assay results to avoid over- and under-treating.
CONCLUSION
CDI should be considered in all patients with traditional risk factors. Heightened clinical suspicion of CDI is required in patients with hypogammaglobulinemia, transplant recipients, patients with gastrointestinal surgical history, and inflammatory bowel disease. Testing should be limited to patients with clinical manifestations of CDI to ensure a high pretest probability for test interpretation. Healthcare workers should adhere to testing algorithms to optimize yield in the appropriate clinical context. Diagnostic assays should follow a sequential, stepwise approach to categorize the toxin expression status of the bacteria accurately.
PubMed: 38800338
DOI: 10.7759/cureus.59016