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Objective This study aimed to evaluate the burden and trends of paralytic ileus and bowel obstruction in individuals aged ≥ 65 years, offering insights into prevention, treatment, and healthcare policy. Methods Data from the Global Burden of Disease Study 2021 were used to analyze paralytic ileus and intestinal obstruction by demographics, year, country/region, and Socio-Demographic Index (SDI). The statistical methods included Joinpoint regression, decomposition analysis, and Bayesian Age-Period-Cohort modeling. Results In 2021, the global age-standardized incidence of paralytic ileus and intestinal obstruction among the elderly was 643.45 cases per 100,000 individuals. The corresponding prevalence was 24.05 per 100,000 individuals, with disability-adjusted life years (DALYs) of 294.01 per 100,000 person-years and a mortality rate of 20.55 per 100,000 individuals. Between 1990 and 2021, the age-standardized incidence and prevalence of paralytic ileus and intestinal obstruction in the elderly gradually increased, while age-standardized DALYs and mortality consistently declined. Despite similar trends observed across both genders, the disease burden increased with age and was more pronounced in males than in females. Furthermore, the age-standardized incidence and prevalence of these conditions increased with SDI, whereas mortality and DALYs decreased. By 2030, the incidence and prevalence are expected to continue increasing, whereas mortality and DALYs are expected to decrease. Conclusions Despite the consistent decrease in mortality and DALYs associated with paralytic ileus and bowel obstruction in the elderly population aged ≥ 65 years, their incidence and prevalence continue to increase annually. This underscores the importance of improving preventive measures, early screening, and treatment efforts to address this pressing public health challenge.

Purpose Mitochondrial DNA (mtDNA) depletion syndrome (MDDS) encompasses a group of genetic disorders of mtDNA maintenance. Mutation of RRM2B is an uncommon cause of infantile-onset encephalomyopathic MDDS. Here we describe the natural history of this disease. Methods Multinational series of new genetically confirmed cases from six pediatric centers. Results Nine new cases of infantile-onset RRM2B deficiency, and 22 previously published cases comprised a total cohort of 31 patients. Infants presented at a mean of 1.95 months with truncal hypotonia, generalized weakness, and faltering growth. Seizures evolved in 39% at a mean of 3.1 months. Non-neurological manifestations included respiratory distress/failure (58%), renal tubulopathy (55%), sensorineural hearing loss (36%), gastrointestinal disturbance (32%), eye abnormalities (13%), and anemia (13%). Laboratory features included elevated lactate (blood, cerebrospinal fluid (CSF), urine, magnetic resonance (MR), spectroscopy), ragged-red and cytochrome c oxidase–deficient fibers, lipid myopathy, and multiple oxidative phosphorylation enzyme deficiencies in skeletal muscle. Eight new RRM2B variants were identified. Patients with biallelic truncating variants had the worst survival. Overall survival was 29% at 6 months and 16% at 1 year. Conclusions Infantile-onset MDDS due to RRM2B deficiency is a severe disorder with characteristic clinical features and extremely poor prognosis. Presently management is supportive as there is no effective treatment. Novel treatments are urgently needed.

The burden of paralytic ileus (PI) in the intensive care unit remains high, and the Charlson Comorbidity Index (CCI) is strongly associated with the prognosis of several acute and chronic diseases. However, evidence specifically evaluating the prognostic value of CCI in intensive care unit patients with PI remains limited. This study aimed to investigate the association between CCI and clinical prognosis in critically ill patients with PI. In this study, data were extracted from the Medical Information Mart for Intensive Care IV (version 2.2), a large, publicly available critical care database, and used to determine the optimal cut-off value of CCI for predicting mortality in patients with PI using the receiver operating characteristic curves, and the association between CCI and mortality was evaluated using Cox regression and restricted cubic spline analysis. A machine learning (ML) prediction model was then constructed to predict hospital mortality by combining CCI and other clinical characteristics. The study included 863 patients with PI (age: median 65.4, IQR 54.6-75.5 y; male: 575/863, 66.6%). The receiver operating characteristic curve identified an optimal cut-off value of 4.5 for CCI. The multivariate Cox regression analysis showed that compared to the lowest CCI quartile, patients with elevated CCI levels were more likely to have elevated hospital (Q4: hazard ratio [HR] 2.447, 95% CI 1.210-4.951), 28-day (Q4: HR 3.891, 95% CI 1.956-7.740), and 90-day (Q4: HR 3.994, 95% CI 2.224-7.173) all-cause mortality were significantly associated with elevated CCI levels; however, the association with ICU mortality (Q4: HR 1.892, 95% CI 0.653-5.480) was weak. Among the 11 ML models, the light gradient boosting machine model performed best, with internal validation results showing an area under the curve of 0.811, a geometric mean of 0.670, and an F1-score of 0.895. The CCI is an important predictor of hospital, 28-day, and 90-day all-cause mortality in critically ill patients with PI, and the optimal threshold is 4.5. ML models, including the CCI, show high accuracy in predicting hospital mortality, and the CCI occupies an important position in the model. This suggests that the CCI helps to identify high-risk patients, supports clinical decision-making, and improves prognosis.

Chronic intestinal pseudo-obstruction (CIPO) is a rare, disabling disorder responsible for motility-related intestinal failure. Because it induces malnutrition, CIPO is a significant indication for home parenteral nutrition (HPN). The objective of the study was to evaluate long-term outcome of CIPO patients requiring HPN during adulthood. In total, 51 adult CIPO patients (18 men/33 women, median age at symptom occurrence 20 (0-74) years, 34/17 primary/secondary CIPO) followed up at our institution for HPN management between 1980 and 2006 were retrospectively studied for survival and HPN dependence rates using univariate and multivariate analysis. Follow-up after diagnosis was 8.3 (0-29) years. Surgery was required in 84% of patients. The number of interventions was 3 +/- 3 per patient (mean +/- s.d.), leading to short bowel syndrome in 19 (37%) patients. Actuarial survival probability was 94, 78, 75, and 68% at 1, 5, 10, and 15 years, respectively. Multivariate analysis showed that lower mortality was associated with the ability to restore oral feeding at baseline (hazard ratio (HR) = 0.2 (0.06-0.65), P = 0.008) and symptom occurrence before the age of 20 years (HR=0.18 (0.04-0.88), P = 0.03). Higher mortality was associated with systemic sclerosis (HR=10.4 (1.6-67.9), P = 0.01). Actuarial HPN dependence was 94, 75, and 72% at 1, 2, and 5 years, respectively. In this large cohort of CIPO adult patients with severe intestinal failure, i.e., those requiring HPN, we found a higher survival probability than previously reported. These results should be taken into account when considering intestinal transplantation.

Background—Chronic idiopathic intestinal pseudo-obstruction, a syndrome of ineffectual motility due to a primary disorder of enteric nerve or muscle, is rare. Aims—To determine the clinical spectrum, underlying pathologies, response to treatments, and prognosis in a consecutive unselected group of patients. Methods—Cross sectional study of all patients with clinical and radiological features of intestinal obstruction in the absence of organic obstruction, associated with dilated small intestine (with or without dilated large intestine), being actively managed in one tertiary referral centre at one time. Results—Twenty patients (11 men and nine women, median age 43 years, range 22–67) fulfilled the diganostic criteria. Median age at onset of symptoms was 17 years (range two weeks to 59 years). Two patients had an autosomally dominant inherited visceral myopathy. Major presenting symptoms were pain (80%), vomiting (75%), constipation (40%), and diarrhoea (20%). Eighteen patients required abdominal surgery, and a further patient had a full thickness rectal biopsy. The mean time interval from symptom onset to first operation was 5.8 years. Histology showed visceral myopathy in 13, visceral neuropathy in three, and was indeterminate in three. In the one other patient small bowel motility studies were suggestive of neuropathy. Two patients died within two years of symptom onset, one from generalised thrombosis and the other from an inflammatory myopathy. Of the remaining 18 patients, eight were nutritionally independent of supplements, two had gastrostomy or jejunostomy feeds, and eight were receiving home parenteral nutrition. Five patients were opiate dependent, only one patient had benefited from prokinetic drug therapy, and five patients required formal psychological intervention and support. Conclusions—In a referral setting visceral myopathy is the most common diagnosis in this heterogeneous syndrome, the course of the illness is usually prolonged, and prokinetic drug therapies are not usually helpful. Ongoing management problems include pain relief and nutritional support.

BACKGROUND Children with chronic intestinal pseudo-obstruction (CIPO) often require total parenteral nutrition (TPN) which puts them at risk of liver failure and recurrent line infections. Intestinal transplantation has become a therapeutic option for TPN dependent children with intestinal failure who are failing management with TPN. AIMS To investigate the outcome of children with CIPO referred for intestinal transplantation. METHODS A retrospective review was carried out of records and diagnostic studies from 27 patients with CIPO referred for intestinal transplantation. RESULTS Five children were not listed for transplantation: two because of parental decision, two because of suspicion of Munchausen syndrome by proxy, and one because he tolerated enteral nutrition. Six are still TPN dependent and awaiting transplantation. Eight children died awaiting transplantation. Eight children underwent transplantation. Three died (two months, seven months, and four years after transplant). Five children are alive with a median follow up of 2.6 years (range two months to six years). All transplanted children were able to tolerate full enteral feedings. The postoperative course was complicated by dumping syndrome, Munchausen syndrome by proxy, narcotic withdrawal, and uncovering of achalasia.Conclusion—Intestinal transplantation may be a life saving procedure in children with CIPO. Early referral and thorough pretransplant evaluation are keys to successful transplantation.

Hepatocyte growth factor/scatter factor (HGF/SF) can stimulate growth of gastrointestinal epithelial cells in vitro ; however, the physiological role of HGF/SF in the digestive tract is poorly understood. To elucidate this in vivo function, mice were analyzed in which an HGF/SF transgene was overexpressed throughout the digestive tract. Nearly a third of all HGF/SF transgenic mice in this study (28 of 87) died by 6 months of age as a result of sporadic intestinal obstruction of unknown etiology. Enteric ganglia were not overtly affected, indicating that the pathogenesis of this intestinal lesion was different from that operating in Hirschsprung's disease. Transgenic mice also exhibited a rectal inflammatory bowel disease (IBD) with a high incidence of anorectal prolapse. Expression of interleukin-2 was decreased in the transgenic colon, indicating that HGF/SF may influence regulation of the local intestinal immune system within the colon. These results suggest that HGF/SF plays an important role in the development of gastrointestinal paresis and chronic intestinal inflammation. HGF/SF transgenic mice may represent a useful model for the study of molecular mechanisms associated with a subset of IBD and intestinal pseudo-obstruction. Moreover, our data identify previously unappreciated side effects that may be encountered when using HGF/SF as a therapeutic agent.

The immune checkpoint inhibitors (ICIs)-induced anti-Hu antibody-associated gastrointestinal pseudo-obstruction (GIPO) is a paraneoplastic neurological syndrome related to autoantibodies. It has a very low incidence but a high mortality rate. This report presents the case of a patient with extensive-stage small-cell lung cancer who developed recurrent bowel obstruction symptoms following ICI therapy. Colonoscopy and abdominal CT tomography failed to identify the underlying cause. A definitive diagnosis of GIPO was made based on the histological findings from an exploratory laparotomy and serum levels of paraneoplastic antibodies. Despite treatment with corticosteroids, no significant improvement was detected in the symptoms, and the patient ultimately died. This case highlights the challenges of managing this rare complication. When unexplained bowel obstruction occurs during ICI therapy, antineuronal antibody testing should be performed to exclude GIPO, as early identification and intervention can reduce mortality.

Abstract Paediatric intestinal pseudo-obstruction (PIPO) encompasses a group of rare disorders in which patients present with the clinical features of bowel obstruction in the absence of mechanical occlusion. The management of PIPO presents a challenge as evidence remains limited on available medical and surgical therapy. Parenteral nutrition is often the mainstay of therapy. Long-term therapy may culminate in life-threatening complications including intestinal failure-related liver disease, central line thrombosis and sepsis. Intestinal transplantation remains the only definitive cure in PIPO but is a complex and resource-limited solution associated with its own morbidity and mortality. We conducted a scoping review to present a contemporary summary of the epidemiology, aetiology, pathophysiology, diagnosis, management and complications of PIPO.Conclusion: PIPO represents a rare disorder that is difficult to diagnose and challenging to treat, with significant morbitity and mortality. The only known cure is intestinal transplantation.What is Known:• Paediatric intestinal pseudo-obstruction is a rare, heterogeneous disorder that confers a high rate of morbidity and mortality• Complications of paediatric intestinal pseudo-obstruction include chronic pain, small intestine bacterial overgrowth and malrotation. Other complications can occur related to its management, such as line infections with parenteral nutrition or cardiac side effects of prokinetic medicationsWhat is New:• Progress in medical and surgical therapy in recent years has led to improved patient outcomes• Enteral autonomy has been reported in most patients at as early as 1 month post-transplantation

Background: In the United States, ileus accounts for USD 750 million of healthcare expenditures annually and significantly contributes to morbidity and mortality. Despite its significance, the complete picture of mortality risk factors for these patients have yet to be fully elucidated; therefore, the aim of this study is to identify mortality risk factors in patients emergently admitted with paralytic ileus. Methods: Adult and elderly patients emergently admitted with paralytic ileus between 2005–2014 were investigated using the National Inpatient Sample Database. Clinical outcomes, therapeutic management, demographics and comorbidities were collected. Associations between mortality and all other variables were established via univariable and multivariable logistic regression models. Results: A total of 81,674 patients were included, of which 45.2% were adults, 54.8% elderly patients, 45.8% male and 54.2% female. The average adult and elderly ages were 48.3 and 78.8 years, respectively. Elderly patients displayed a significantly (p < 0.01) higher mortality rate (3.0%) than adults (0.7%). The final multivariable logistic regression model showed that for every one-day delay in operation, the odds of mortality for adult and elderly patients increased by 4.1% (p = 0.002) and 3.2% (p = 0.014), respectively. Every additional year of age corresponded to 3.8% and 2.6% increases in mortality for operatively managed adult (p = 0.026) and elderly (p = 0.015) patients. Similarly, non-operatively treated adult and elderly patients displayed associations between mortality and advanced age (p = 0.001). The modified frailty index exhibited associations with mortality in operatively treated adults, conservatively managed adults and conservatively managed elderly patients (p = 0.001). Every additional day of hospitalization increased the odds of mortality in non-operative adult and elderly patients by 7.6% and 5.8%, respectively. Female sex correlated to lower mortality rates in non-operatively managed adult patients (odds ratio = 0.71, p = 0.028). Undergoing invasive diagnostic procedures in non-operatively managed elderly patients related to reduced mortality (odds ratio = 0.78, p = 0.026). Conclusions: Patients emergently admitted for paralytic ileus with increased hospital length of stay, longer time to operation, advanced age or higher modified frailty index displayed higher mortality rates. Female sex and invasive diagnostic procedures were negatively correlated with death in nonoperatively managed patients with paralytic ileus.