Background: Aberrant activation of autophagy (proteinopathy) leads to neurodegeneration in various neurological disorders. Results: Compensatory basal autophagy is activated, and genotoxins deregulate autophagy in the ubiquitin pathway-compromised ataxia telangiectasia (A-T) cells. Conclusion: Deregulation of autophagy is due to the elevated expression of ISG15 in A-T cells. Significance: Results highlight a causal contribution of a novel "ISG15 proteinopathy" in A-T neurodegeneration.
Background: Studies of adult and pediatric patients undergoing appendectomy have reported variable outcomes and operative metrics related to the effect of obesity. The purpose of this study was to investigate the effect of obesity in adult and pediatric patients undergoing appendectomy at our institution. Methods: This single-center retrospective study evaluated the relationship between length of hospital stay for appendectomy and body mass index (BMI). Data obtained from the electronic medical record included age, sex, weight, height, BMI, the number of hours the patient experienced symptoms prior to presentation to the emergency room, the number of hours the patient was admitted prior to surgery, the number of hours of hospital admission after surgery, perforated appendix, preoperative comorbidities, and evidence of preoperative sepsis. Results: During the 3-year study period, 118 adults and 38 children who underwent appendectomy composed the study groups. Patients were stratified by obese and nonobese, with obesity defined as BMI ࣙ30.0 kg/m 2. In adults, we found no significant difference between length of stay in obese (n=45) and nonobese (n=73) patients (79.6 ± 65.5 hours vs 101.6 ± 123.0 hours; P=0.21). In children, we found no significant difference between length of stay in obese (n=9) and nonobese (n=29) patients (92.9 ± 64.6 hours vs 109.0 ± 93.5 hours; P=0.54). Conclusion: Obesity did not affect length of stay in adults and children who underwent appendectomy in the present series.
Benign recurrent intrahepatic cholestasis represents a rare class of autosomal recessive chronic cholestasis disorders, usually presenting with recurrent episodes of intense pruritus and jaundice. We report a 27-year-old woman presenting with benign recurrent intrahepatic cholestasis type 2 due to heterozygosity in ABCB11. Interestingly, she was also found to be heterozygous in cystic fibrosis transmembrane conductance regulator, NPHP4, and A1ATD (SERPINA1), which may explain the severe nature of her disease expression because heterozygosity in each of these genes has been associated with cholestasis. Finally, she exhibited a response to steroids that may have implications for future treatment of bile salt export pump-related diseases.
Background: This study aimed to aid in risk assessment of pediatric endoscopic retrograde cholangiopancreatography (ERCP) candidates by utilizing a national pediatric database with a large sample to assess how patient characteristics may affect ERCP complication rates.
Methods:The Kids' Inpatient Database (KID) is a sample of pediatric discharges in states participating in the Healthcare Cost and Utilization Project (HCUP). This database provides demographic information, hospitalization duration, and outcome information for hospitalizations during which an ERCP occurred. International Classification of Diseases (ICD) codes were used to determine the hospitalization indication. ERCP complication rate was ascertained via ICD codes. All statistical analyses were performed using SAS 9.4.
Results:Complications were seen in 5.4% of hospitalizations with mortality observed in less than 0.2%. This analysis captured a large Hispanic population, specifically in the South and West regions. Gallbladder calculus and cholecystitis were more likely to occur in females. A higher percentage of patients in the age 10 -17 group were female (72.2% vs. 52.7%, P < 0.01) and Hispanic (33.4% vs. 22.7%, P < 0.01) compared to the age 0 -9 group. Age 0 -5 and male gender were associated with lower routine home discharge rates and longer lengths of stay. Complications occurred at a higher rate in ages 0 -5, though the difference was not statistically significant.Conclusions: ERCP is a safe procedure for pediatric patients with low complication rates and rare mortality. We found statistically significant differences in the procedure indications between pediatric age groups, races, and genders. Age ≤ 5 years and male gender were associated with more complicated healthcare courses.
INTRODUCTION:
Evidence supports an association between CNS demyelination disorders and use of with Tumor Necrosis Factor-α (TNF-α) inhibitors. Here we present a case of optic neuritis onset after initiating therapy with infliximab-dyyb and describe subsequent treatment response.
CASE DESCRIPTION/METHODS:
A 31-year-old female with a history of Ulcerative Colitis, presented with new left periorbital heaviness 2 weeks after receiving the first dose of infliximab-dyyb. The pain eventually progressed to darkening and blurring of vision. The physical examination was positive for reduced visual acuity, color desaturation, and positive relative afferent pupillary reflex on the left eye only. CSF studies were remarkable for positive Oligoclonal bands and increased IgG Index. Orbital and brain MRI were suggestive of optic neuritis. Infliximab-dyyb was discontinued and she was treated with a course of IV Methylprednisolone and discharged home on Glatiramir acetate. On follow up visits, eye pain and blurry vision dramatically improved. In order to avoid extra-colonic side effects, she was switched to vedolizumab which she has tolerated well.
DISCUSSION:
It has been described that IBD patients can present with CNS demyelination, which can be explained by both conditions sharing epidemiological and immunological characteristics. However, this association can be confounded by the use of TNF-α inhibitors, which are commonly used in treating IBD and have been themselves associated with CNS demyelination. Though mechanism is unclear, blocking TNF-α receptors in the CNS has been found to result in neuroinflammation and long-term neural damage. The average time from exposure to the onset of symptoms has been described as seventeen months in one case series on infliximab. However, in our patient she started experiencing symptoms after the initial dose. This rapid reaction may be due to infliximab-dyyb being used. To our knowledge this is the first reported reaction related to a bio-similar. This demonstrates that further studies are needed to estimate the true incidence of demyelinating disorders in patients with IBD and to elucidate if bio-similar may be subject to stronger demyelinating reactions.
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