The management of treatment-resistant schizophrenia (TRS) is challenging as the medications involved, often atypical antipsychotics, have a host of associated adverse effects. While complications such as agranulocytosis are well established and necessitate close hematological monitoring, the gastrointestinal effects of particular atypical antipsychotics, such as clozapine, are recognized to a lesser extent. The following case of TRS leading to chronic treatment-resistant pseudo-obstruction, eventually requiring total colectomy, highlights the considerable sequelae of clozapine on the gastrointestinal tract. Beyond the effects of severe constipation, the possible implications of ischemic colitis, stercoral perforation, and intraabdominal sepsis warrant a degree of caution when prescribing such medication. This study sheds light on the importance of monitoring bowel motility when administering antipsychotics, particularly clozapine, to avoid these deleterious consequences.

Chronic intestinal pseudo-obstruction is a rare and heterogeneous syndrome characterized by recurrent symptoms of intestinal obstruction with radiological features of dilated small or large intestine with air/fluid levels in the absence of any mechanical occlusive lesion. Several diseases may be associated with chronic intestinal pseudo-obstruction and in these cases, the prognosis and treatment are related to the underlying disease. Also, in its \"primary or idiopathic\" form, two subgroups of patients should be determined as they require a more specific therapeutic approach: patients whose chronic intestinal pseudo-obstruction is due to sporadic autoimmune/inflammatory mechanisms and patients whose neuromuscular changes are genetically determined. In a context of a widely heterogeneous adult population presenting chronic intestinal pseudo-obstruction, this review aims to summarize a practical diagnostic workup for identifying definite subgroups of patients who might benefit from more specific treatments, based on the etiology of their underlying condition.

Duchenne muscular dystrophy is a progressive muscle wasting disease caused by pathogenic variants in DMD. Gastrointestinal involvement is increasingly recognised in older patients and can manifest as life-threatening bowel dysmotility. We describe a series of adults with Duchenne muscular dystrophy who developed either severe colonic pseudo-obstruction or sigmoid volvulus requiring urgent assessment and intervention. The presentations varied in their clinical picture and outcomes, but together highlight the complexity of managing gastrointestinal complications in this cohort of patients. Key considerations include pre-existing cardiorespiratory compromise and the increased risk associated with surgery and general anaesthesia. We also outline a role for home parenteral nutrition in the long-term management of associated bowel dysmotility.

Percutaneous endoscopic colostomy (PEC) tube placement is a minimally invasive procedure used to treat recurrent colonic pseudo-obstruction, sigmoid volvulus, chronic intractable constipation, and neurogenic bowel. PEC is a viable treatment alternative for patients who have failed conservative therapies and are deemed high risk for surgical management. We present a case of acute colonic pseudo-obstruction after Clostridioides difficile infection that was unresponsive to medical treatment or endoscopic decompression. A PEC tube was placed into the transverse colon with successful resolution of the colonic distension.

Ogilvie\'s syndrome is a condition characterized by colonic dilation in the absence of mechanical obstruction. This case report presents a patient who was immobile and hospitalized for several months following a motor vehicle accident that left the patient paralyzed, who subsequently developed Ogilvie\'s syndrome. The aim of this study is to briefly discuss the clinical presentation, diagnostic workup, and management of Ogilvie\'s syndrome. This article also discusses the impact of narcotics and the possible association with Ogilvie\'s syndrome in this patient.

Pitt-Hopkins syndrome (PTHS) is a rare, neurodevelopmental genetic disorder caused by mutations in the TCF4 gene. This gene encodes a ubiquitous, class I, basic helix-loop-helix factor, which is implicated in various developmental and regulatory processes. Predominant clinical manifestations of PTHS include facial dysmorphisms, intellectual disability, absence of expressive language, epilepsy, as well as visual and musculoskeletal impairments. Gastrointestinal (GI) complications, such as chronic intestinal pseudo-obstruction, gastroparesis with delayed bowel transit, chronic constipation culminating in failure to thrive, and gastroesophageal reflux disease (GERD), are also prevalent in these patients. The early identification of pain etiology in PTHS patients poses a significant clinical challenge. This report presents two cases of PTHS patients suffering from gastrointestinal dysmotility, evaluated at our Pediatrics Clinic at the \"Microcitemico\" Hospital. A review of existing literature was conducted via the PubMed database to elucidate the current understanding of the GI phenotype in PTHS. Twenty articles were deemed most relevant and selected for this purpose. In both patients, severe constipation and abdominal distension resulted in persistent agitation and inconsolable crying. These distress symptoms were completely ameliorated following prompt pharmacological intervention.

OBJECTIVE: Acute Colonic Pseudo-obstruction (ACPO) is a cause of large intestinal dilation and obstruction without any physical transition point. It remains difficult to diagnose and treat. We review the recent updates on diagnosis and management of ACPO.
RESULTS: Recent guidelines have posited that conservative management can be tried in most cases of ACPO, but that early decompression and surgery should be considered. Use of neostigmine is still a viable option but there is also promising data on pyridostigmine as well as prucalopride. Resolution of ACPO should be followed by daily use of polyethylene glycol (PEG) to help prevent recurrence. ACPO warrants early and accurate diagnosis with exclusion of alternate causes of large bowel dilation. Conservative management can be attempted for 48-72 h in those with cecal diameters < 12 cm and without signs of peritonitis and perforation. Early escalation of management should be attempted with neostigmine followed by endoscopy and/or surgery as needed, given that longer periods of dilation are associated with worse outcomes. There is promising new evidence for use of pyridostigmine and prucalopride, but further trials are needed prior to incorporating them into regular use. Finally, studies are lacking regarding prevention of ACPO after initial resolution.

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Visceral smooth muscle cells (SMCs) are an integral component of the gastrointestinal (GI) tract that regulate GI motility. SMC contraction is regulated by posttranslational signaling and the state of differentiation. Impaired SMC contraction is associated with significant morbidity and mortality, but the mechanisms regulating SMC-specific contractile gene expression, including the role of long noncoding RNAs (lncRNAs), remain largely unexplored. Herein, we reveal a critical role of Carmn (cardiac mesoderm enhancer-associated noncoding RNA), an SMC-specific lncRNA, in regulating visceral SMC phenotype and contractility of the GI tract.
Genotype-Tissue Expression and publicly available single-cell RNA sequencing (scRNA-seq) data sets from embryonic, adult human, and mouse GI tissues were interrogated to identify SMC-specific lncRNAs. The functional role of Carmn was investigated using novel green fluorescent protein (GFP) knock-in (KI) reporter/knock-out (KO) mice. Bulk RNA-seq and single nucleus RNA sequencing (snRNA-seq) of colonic muscularis were used to investigate underlying mechanisms.
Unbiased in silico analyses and GFP expression patterns in Carmn GFP KI mice revealed that Carmn is highly expressed in GI SMCs in humans and mice. Premature lethality was observed in global Carmn KO and inducible SMC-specific KO mice due to GI pseudo-obstruction and severe distension of the GI tract, with dysmotility in cecum and colon segments. Histology, GI transit, and muscle myography analysis revealed severe dilation, significantly delayed GI transit, and impaired GI contractility in Carmn KO vs control mice. Bulk RNA-seq of GI muscularis revealed that loss of Carmn promotes SMC phenotypic switching, as evidenced by up-regulation of extracellular matrix genes and down-regulation of SMC contractile genes, including Mylk, a key regulator of SMC contraction. snRNA-seq further revealed SMC Carmn KO not only compromised myogenic motility by reducing contractile gene expression but also impaired neurogenic motility by disrupting cell-cell connectivity in the colonic muscularis. These findings may have translational significance, because silencing CARMN in human colonic SMCs significantly attenuated contractile gene expression, including MYLK, and decreased SMC contractility. Luciferase reporter assays showed that CARMN enhances the transactivation activity of the master regulator of SMC contractile phenotype, myocardin, thereby maintaining the GI SMC myogenic program.
Our data suggest that Carmn is indispensable for maintaining GI SMC contractile function in mice and that loss of function of CARMN may contribute to human visceral myopathy. To our knowledge this is the first study showing an essential role of lncRNA in the regulation of visceral SMC phenotype.

123-Iodine metaiodobenzylguanidine (I-123 MIBG) imaging is frequently used in the assessment of sympathetic innervation and autonomic dysfunction in patients with cardiac failure, neurodegenerative Parkinson\'s syndrome, multiple system atrophy, myotonic dystrophy, and diabetic mellitus. The etiology of pseudo-obstruction remains unknown with likely imbalance between sympathetic and parasympathetic innervation proposed as a hypothesis. We present a case demonstrating the utility of I-123 MIBG scintigraphy for evaluating a case of pseudo-obstruction requiring frequent hospitalization due to progressive complex autoimmune neurological disorder.