Pseudomembranous colitis due to Clostridioides difficile infection (CDI) is a serious complication of antibiotic therapy and hospitalization that can progress to toxic megacolon, necessitating emergency colectomy. Patients undergoing pancreaticoduodenectomy (PD) are particularly at high risk due to biliary obstruction, recurrent cholangitis, broad-spectrum antibiotic exposure, and prolonged postoperative stays. We report the case of an elderly woman with multiple cardiovascular comorbidities and recent CDI who underwent PD for pancreatic ductal adenocarcinoma (PDAC). Prior to surgery, she had an endoscopic retrograde cholangiopancreatography (ERCP) with duodenobiliary (DB) stent placement due to obstructive jaundice, and biopsies confirmed PDAC. Intravenous cefotaxime was initiated because of signs of acute cholangitis. She subsequently developed CDI and completed treatment with oral vancomycin, which was discontinued only 11 days before the PD. Standard prophylaxis with cefazolin was administered prior to surgery. On postoperative day (POD) 1, empirical antibiotic therapy with cefotaxime was initiated. By POD 3, she developed profuse watery diarrhea, fever, and leukocytosis, with confirmed recurrent CDI. Despite prompt fidaxomicin therapy and intensive care, she rapidly deteriorated. Computed tomography (CT) revealed severe pancolitis and toxic megacolon. Emergency subtotal colectomy with end ileostomy was performed, and histopathological examination confirmed the diagnosis. She eventually stabilized but remained frail, and the tumor board recommended best supportive care instead of adjuvant chemotherapy due to the disease stage and the severe course of CDI. This case underscores the need for early CDI testing in postoperative diarrhea following PD and for cautious perioperative antibiotic strategies in patients with recent CDI, as broad-spectrum antibiotics may precipitate fulminant recurrence.

Clostridioides difficile is a toxin-producing pathogen that opportunistically infects those with a depleted gut microbiome, often triggered by antibiotic use. C. difficile preferentially utilizes Stickland amino acids, including proline, to promote energy generation and growth for colonization. We evaluated host outcomes from infection with wild-type and ΔprdB mouse-infective C. difficile ATCC 43255 strains to investigate how proline metabolism modulates C. difficile's pathogenesis and interactions with commensals in an enriched gut nutrient environment. While gnotobiotic mice infected with the ΔprdB mutant succumbed to infection, they showed delayed colonization and toxin production, thereby extending their survival. In vivo C. difficile transcriptomic analyses demonstrated a shift from Stickland fermentation to carbohydrate metabolism in the ΔprdB mutant. To investigate functions of C. difficile's proline reductase in interactions with the commensal microbiota, we evaluated infection outcomes in mice co-colonized with the disease-promoting commensal Clostridium sardiniense (CSAR). One-third of CSAR and ΔprdB-infected mice survived, while co-colonized mice with the wild-type strain rapidly succumbed within 48 h. In vivo transcriptomic analyses from co-colonized mice identified additional metabolic defects in the ΔprdB mutant, including failure to express oxidative Stickland pathways and ornithine fermentations to harness CSAR-produced ornithine, suggesting conversion of the mutant into a glycolytic strain that was now in direct competition with CSAR for carbohydrate substrates. CSAR remained metabolically active during the ΔprdB infection through its mucin degradation and polysaccharide and disaccharide metabolism. Our findings illustrate critical functions of C. difficile's proline reductase in coordinating early metabolism to facilitate gut colonization, including interactions with a cross-feeding commensal species.

The formation of the enteric nervous system (ENS) primarily involves the migration of enteric neural crest-derived cells (ENCCs) and the subsequent maturation of enteric neurons. The developmental dysfunction of ENCCs and enteric neurons can result in ENS disorders, such as hypoganglionosis (HG). Although neurite outgrowth is fundamental to neuronal maturation, the mechanisms by which neurite outgrowth influences neuronal maturation remain poorly defined. Here, we identified EMB as a critical regulator of enteric neuronal maturation. In EMB mutant patients, the expression of EMB is reduced in the enteric neurons of the HG-affected colon. In mice, knockdown of Emb exhibited HG-like features and defects. In vitro experiments, along with analyses using Smart-seq2 and immunoprecipitation-mass spectrometry, demonstrated that EMB is essential for autophagic flux and physically interacts with ATG7, recruiting it to the autophagosomal membrane to facilitate autophagosome formation, and then EMB/ATG7-mediated autophagy promotes neurite outgrowth. Our findings elucidate EMB-mediated autophagy as a pivotal pathway in regulating neurite outgrowth and promoting the maturation of enteric neurons, which provides a mechanistic basis for understanding ENS disorders.

Congenital central hypoventilation syndrome (CCHS) and Hirschsprung's disease (HD) belong to neurocristopathies - autonomic nervous system defects caused by abnormal neural crest cells migration. Their co-occurrence defines Haddad Syndrome (HS) associated also with increased risk of neural crest origin tumors, mainly neuroblastoma (NBL), and PHOX2B gene mutation. This case concerns a male newborn presenting respiratory failure minutes after birth. Due to sleep apnea and increasing hypercapnia, he required intubation. Genetic testing revealed an anomaly in PHOX2B gene. In subsequent days, the patient did not pass the meconium, which, based on the imaging tests and biopsy, raised a suspicion of HD. The boy was diagnosed with HS and additional diagnostic measures, including cancer screening, were ordered, owing to the syndrome's characteristics. Awareness of such conditions enables clinicians to implement targeted management that may significantly improve long-term outcomes and quality of life for affected children.

Hirschsprung disease (HSCR) is a congenital intestinal motility disorder characterized by the absence of enteric neurons in the distal bowel. Compared with bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq) enables gene expression profiling at the single-cell level, resolving cellular heterogeneity that is masked in population-averaged analyses. A standardized scRNA-seq workflow was established to characterize the transcriptional landscape of ganglionic and aganglionic segments from patients with HSCR. Colon tissues were collected, and hematoxylin and eosin staining was performed to identify ganglionic and aganglionic regions. Tissues were enzymatically and mechanically dissociated into single-cell suspensions, followed by filtration, viability assessment, and construction of single-cell transcriptome libraries. Libraries that passed quality control were sequenced, and raw data were processed for cell quantification and quality filtering to remove low-quality cells and technical artifacts. After normalization and dimensionality reduction, cells were clustered and annotated based on established marker genes. Downstream analyses compared cell-type composition between ganglionic and aganglionic tissues and identified differentially expressed genes within key immune cell subsets. The results reveal substantial differences in the immune microenvironment between ganglionic and aganglionic segments in HSCR.

Although cytomegalovirus (CMV) seropositivity is common in the general population, primary CMV infection in immunocompetent adults is usually asymptomatic or causes only a mild mononucleosis-like illness, and severe symptomatic or tissue-invasive disease is uncommon. CMV colitis may present with nonspecific symptoms, delaying recognition, particularly in immunocompetent patients in whom clinical suspicion is often low. Delayed diagnosis may allow progression to serious complications, including gastrointestinal bleeding, perforation, toxic megacolon, and, less commonly, stricture formation. We report a case of CMV colitis in an immunocompetent woman presenting with a colonic stricture initially presumed to be malignant rather than with the more typical features of abdominal pain, diarrhea, fever, and hematochezia. This case emphasizes the diagnostic challenge of CMV colitis in patients without classic risk factors, particularly when it mimics colonic malignancy and requires tissue diagnosis because noninvasive testing may not reliably exclude disease.

Goldberg-Shprintzen megacolon syndrome (GOSHS) is a rare autosomal recessive neurodevelopmental disorder characterized by Hirschsprung disease, microcephaly, neurodevelopmental impairment, and craniofacial dysmorphism. We report a male neonate born at 35+4 weeks of gestation who presented on day 4 of life with abdominal distension and delayed passage of meconium. Clinical examination revealed microcephaly, generalized hypotonia, craniosynostosis, and dysmorphic facial features, with a positive family history of GOSHS. Hirschsprung disease was confirmed by rectal biopsy, and cranial imaging demonstrated structural brain abnormalities, including hypoplasia of the corpus callosum, and confirmed the presence of craniosynostosis. Targeted molecular analysis of the Kinesin Family Binding Protein (KIFBP) gene using polymerase chain reaction (PCR) amplification followed by Sanger sequencing identified compound heterozygous pathogenic variants, confirming the diagnosis during the neonatal period. GOSHS should be considered in neonates presenting with Hirschsprung disease in combination with hypotonia, dysmorphic features, or neuroimaging abnormalities. Early molecular diagnosis may facilitate timely multidisciplinary management and genetic counseling.

Clostridioides difficile infection (CDI) typically presents with diarrhea in elderly or antibiotic-exposed patients. We report a 40-year-old immunocompetent man with alcohol use disorder who presented with abdominal pain and jaundice, rapidly progressing to refractory constipation and colonic dilation (14.7 cm) mimicking acute colonic pseudo-obstruction. Conservative management including bowel regimens and neostigmine (generally contraindicated in suspected toxic megacolon) were attempted. Colonoscopic decompression revealed cecal pseudomembranes whereas rest of colon was grossly normal. Stool testing showed discordant results that is, negative toxin enzyme immunoassay but positive stool polymerase chain reaction (Nucleic Acid Amplification Testing), supporting CDI in appropriate clinical context. Despite appropriate broad-spectrum antibiotics and emergent subtotal colectomy for fulminant disease with ischemic changes, he developed septic shock and multiorgan failure. This atypical, fulminant CDI presentation without diarrhea, initially mimicking acute colonic pseudo-obstruction, with isolated cecum and ileum involvement, underscores diagnostic pitfalls and need for early polymerase chain reaction/endoscopy in unexplained megacolon.

Toxic megacolon is a rare and life-threatening complication of ulcerative colitis, representing a medical and surgical emergency with a poor prognosis. We report the case of a 31-year-old man with no significant past medical history, admitted for a 15-day history of bloody mucoid diarrhea associated with general health deterioration. Endoscopic and histopathological findings were consistent with a severe inaugural flare of ulcerative colitis. Despite optimal medical management, the clinical course was marked by the abrupt onset of septic shock. Abdominal imaging revealed acute colonic dilatation consistent with toxic megacolon, leading to an indication for emergency subtotal colectomy. The outcome was unfavorable, with the patient's death occurring in the context of multiorgan failure.