Clinical Case Summary

A 25-year-old man, a law graduate, denied significant medical history, except for an appendectomy in 2014. He was diagnosed with chronic idiopathic ulcerative colitis in 2016 and was previously treated with mesalazine 4.5g every 24 hours. A colonoscopy in 2019 showed pancolitis Mayo 3 (Montreal S2-E3). Due to the lack of response to conventional treatment, prednisone cycles were initiated, and infliximab was started at a dose of 5mg/kg since 2019 with an adequate clinical response. On 12/24/2020, calprotectin was 5149 mcg/g.
In September 2021, he presented with asthenia, adynamia, dizziness, and unquantified fever, so he went to the hospital, where systemic inflammatory response syndrome was evident (tachycardia, fever of 39°C, and leukocytosis, dyspnea). Serial blood cultures and bacilloscopies were negative, and a chest CT scan showed a solid nodule-like pulmonary lesion in the right middle lobe (image 1). In November 2021, a thoracotomy with right middle lobectomy was performed, revealing abundant purulent material and a suggestive lesion of a lung abscess; it was positive for Nocardia farcinica, and histopathological results were positive for Nocardia spp. The patient subsequently developed cerebellar syndrome, and an MRI on November 5, 2021, showed cerebellar abscesses in the left hemisphere and hydrocephalus (image 1), requiring a ventriculoperitoneal shunt placement and surgical decompression, draining abscess, and isolating Nocardia spp.
Directed antibiotic therapy (trimethoprim-sulfamethoxazole) was started and continued until December 2021 with clinical improvement. Anti-TNF was discontinued, and mesalazine, steroid, and azathioprine were continued to maintain clinical remission of the disease without neurological and respiratory sequelae.

References

1. Abreu C, Rocha-Pereira N, Sarmento A, Magro F. Nocardia infections among immunomodulated inflammatory bowel disease patients: A review. World J Gastroenterol. 2015 Jun 7;21(21):6491-8. Doi: 10.3748/wjg.v21.i21.6491. PMID: 26074688; PMCID: PMC4458760.
2. Margalit I, Goldberg E, Ben Ari Y, Ben-Zvi H, Shostak Y, Krause I, Muhsen K. Clinical correlates of nocardiosis. Sci Rep. 2020 Aug 31;10(1):14272. Doi: 10.1038/s41598-020-71214-4. PMID: 32868850; PMCID: PMC7459281.
3. Garner O, Ramirez-Berlioz A, Iardino A, Mocherla S, Bhairavarasu K. Disseminated Nocardiosis Associated with Treatment with Infliximab in a Patient with Ulcerative Colitis. Am J Case Rep. 2017 Dec 21;18:1365-1369. Doi: 10.12659/ajcr.906391. PMID: 29263313; PMCID: PMC5742452.

Disclosure

Patients with Inflammatory Bowel Disease (IBD) undergoing anti-TNFa treatment are at risk of opportunistic infections, including nocardiosis, caused by Nocardia, gram-positive bacteria that can cause local (lung, skin, and brain) or disseminated infections. In the literature, only 11 cases of nocardiosis related to anti-TNFa have been reported¹.TNFa is an important mediator of inflammation for granuloma formation, and Nocardia spp. is one of the pathogens that generate these granulomas². The diagnosis of nocardiosis should have a high clinical suspicion, especially in patients with risk factors, as it is one of the least reported opportunistic infections, in our case, with the use of anti-TNF in the context of IBD. There are no official reports on prevalence and incidence in the literature².
The most frequent sites of dissemination are the lungs and skin, leading to the central nervous system and any organ³. The diagnostic confirmation is made through pathogen isolation in a clinical sample, which was performed through histopathology of a pulmonary segment².
Treatment is based on antimicrobial therapy and restoration of complications, in our case, a segmentectomy was necessary due to pulmonary infection, and a ventriculoperitoneal shunt placement was necessary due to central nervous system involvement. TMP/SMX has been considered the first-line antimicrobial for 50 years², but targeted therapy based on isolation is recommended, with alternatives including amikacin, carbapenems, and third-generation cephalosporins². The response to TMP/SMX was appropriate in this case.

Clinical Case Summary

Introduction: With an incidence of 0.5-1%, jejunal diverticulosis is a rare gastrointestinal pathology, which remains mostly asymptomatic. However 18% of patients present with life-threatening complications like bleeding or perforation.
Case report: We present the case of a 75-year-old patient admitted to the intensive care unit (ICU) with suspected middle gastrointestinal bleeding. The patient presented to the emergency unit with symptoms including recurrent syncope, hematemesis and hematochezia. Additionally, vital signs such as arterial hypotonia and tachycardia were noted, along with the initial hemoglobin value of 5.5 g/dl, which indicated significant blood loss.Because of the unstable hemodynamic situation the patient was transferred to the ICU. For airway protection endotracheal intubation was performed. An enteroscopy detected blood in the stomach, duodenum and jejunum and revealed multiple jejunal diverticula, however without active bleeding. After transfusion of multiple erythrocyte concentrates and administration of cathecolamines, the patient could be stabilized. Despite initial interventions, a recurrence of decreased hemoglobin levels was observed. Computed tomography failed to localize the bleeding. Emergency laparotomy revealed jejunal diverticulosis, necessitating resection of 40 cm of the jejunum. Intraoperative, resection borders could be endoscopically guided. Postoperatively, the patient was successfully extubated and discharged days later.
Conclusion: Localization of small bowel diverticula bleeding can be endoscopically or radiologically achieved, however is often difficult and problematic. Jejunal diverticular bleeding must be suspected in cases of obscure bleeding and therapeutic strategies must be interdisciplinary discussed. Surgical laparotomy represents ultima ratio in these pathology. A precise surgical resection can be achieved using intraoperative endoscopy in such cases.

Clinical Case Summary

A 2-week-old full-term female infant presented to the pediatric emergency department with five days of vomiting, loss of appetite, and bloody stools. Initially fed a cow milk-based formula, she did not gain weight. On admission, she appeared lethargic, with vital signs indicating low blood pressure, elevated heart rate, increased respiratory rate, and a body temperature of 36.6°C. Cold extremities, delayed capillary refill time, and marbled skin were noted. Abdominal examination revealed distension without peritonitis or skin discoloration, and no hepatosplenomegaly was present. Laboratory tests showed metabolic acidosis with an elevated anion gap and high lactate levels. The patient vomited stomach contents and fecal material, prompting the use of a nasogastric tube, which drained extensively. An abdominal x-ray revealed diffuse pneumatosis in the intestinalis without bowel perforation. Managed in the pediatric intensive care unit with nil per os, total parenteral nutrition, and empirical parenteral antibiotics. Blood and urine cultures, as well as stool PCR testing for common viral and bacterial pathogens, were negative. The infant showed improvement after two weeks of conservative treatment, including abdominal X-rays, which revealed normal gas patterns without signs of pneumatosis intestinalis. Introduction of an amino acid-based formula was well-tolerated without recurrence of symptoms.

Pneumatosis intestinalis mainly occurs during the neonatal period and is more common among preterm neonates. The main etiology is necrotizing enterocolitis (NEC). However, it can present among term neonates, infants, children, and even adults. The differential diagnosis is wide, including cow’s milk protein allergy, infectious diseases, trauma, ischemia, child abuse, and intestinal failure.
The working diagnosis of this case was pneumatosis intestinalis secondary to milk protein allergy, which was managed successfully and conservatively without any invasive procedure.

References

1. Im J, Anjum F. Pneumatosis Intestinalis. [Updated 2023 Apr 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK564381/
2. Abramov A, Luks VL, De Bie F, Hwang R, Allukian M 3rd, Nace GW Jr. Pneumatosis intestinalis in children beyond the neonatal period: is it always benign?. Pediatr Surg Int. 2022;38(3):399-407
3. Overman RE Jr, Criss CN, Gadepalli SK. Necrotizing enterocolitis in term neonates: A different disease process? J Pediatr Surg. 2019 Jun;54(6):1143-1146.
4. Narumoto S, Sakamoto S, Uchida H, et al. Necrotizing enterocolitis in the setting of milk allergy after pediatric living donor liver transplantation. Pediatr Transplant. 2018 Feb;22(1).
5. Reppucci ML, Nolan MM, Cooper E, et al. Pneumatosis Intestinalis in Children With Intestinal Failure: The Result of Intestinal Stress From Enteral Feeding?. J Pediatr Gastroenterol Nutr. 2023;76(5):560-565.

Introduction

Hypermobile Ehlers-Danlos syndrome (hEDS) is a hereditary non-inflammatory disorder of connective tissue laxity characterized by joint hyperextensibility in association with musculoskeletal symptoms. The prevalence of gastrointestinal (GI) symptoms, such as abdominal pain, nausea, and constipation is high in hEDS. Research on the relationship between EDS and GI symptoms has mostly been restricted to disorders of the gut-brain axis, whereas the relationship between hEDS and GI dysmotility remains to be clarified.

Aims & Methods

This study aimed to explore antro-duodenal manometry (ADM) patterns in patients with hEDS presenting with GI symptoms.

In a prospective open-label study, patients with hEDS and GI symptoms presumed to be the results of GI dysmotility underwent a 6-hour high resolution ADM. The manometry tracings were analyzed by two investigators (KS and JC) independently. Antral contraction frequency (contractions per minute) < 1.0 was considered as antral hypomotility. Pylorospasm was defined as isolated pyloric pressure waves within 60 minutes postprandial. The following neuropathic enteric patterns were scored: presence of retrograde peristalsis, bursts, clustered contractions, and absence of phase III contractions. Abnormal ADM was defined as having antral hypomotility and/ or pylorospasm and/ or neuropathic enteric patterns.

Results

Fifty patients (48 women, mean age 30.4 ± 11.1 yrs.) were included. At baseline, 74% of patients were dependent on enteral feeding and the mean BMI was 20.4 ± 4.4 kg/m².
Overall, ADM tracings with one or more abnormal patterns were identified in 53% of patients. Antral hypomotility and pylorospasm were detected in 29% and 15% of patients, respectively. Neuropathic enteric patterns were only seen in 17% of patients. In all cases, no more than one neuropathic pattern was identified. Among the observed neuropathic enteric patterns, 15% of patients showed retrograde peristalsis, 13% absence of phase III contractions, and 2% bursts. Clustered contractions were not identified in this cohort.

Conclusion

Hypermobile Ehlers-Danlos patients presenting with gastrointestinal symptoms showed low numbers of abnormal ADM patterns. In particular, enteric dysmotility was observed in only a small minority of cases. Antroduodenal dysmotility therefore does not appear to be a principle pathomechanism in the majority of hEDS cases studied. Further research is needed to understand the mechanisms that underlie GI symptom generation in this population.

Introduction

Advanced chronic liver disease (ACLD) may present in different stages with distinct prognoses. Child-Pugh and MELD scores are commonly used models for predicting liver-related mortality and decompensation, but they have several limitations. An alternative or complementary tool that is simple and cost-effective would be invaluable. Recently, some studies identified a potential role of ammonia in predicting liver-related outcomes.

Aims & Methods

Our primary objective was to explore the predictive role of plasma ammonia levels regarding liver-related complications and mortality. Our secondary aim was to validate a new measure that corrects baseline ammonia levels to the upper limit of normal (AMM-ULN) and test a cut-off which was proposed in the literature to define patients at higher risk of such outcomes (AMM-ULN ≥ 1.4).
This retrospective study included 278 patients with ACLD who had an ammonia measurement in our hospital between 2018 and 2022. ACLD patients were divided into compensated and decompensated stages, with the latter being subdivided into three stages, according to the type of decompensation. Outcomes of liver-related decompensation and mortality were assessed in each group. AMM-ULN was evaluated as a predictor of these outcomes both in compensated and decompensated patients. The predictive accuracy of AMM-ULN was then determined by identifying the best cut-off.

Results

Plasma ammonia levels and AMM-ULN were predictors of hepatic decompensation (HR = 1.453, 95%CI 1.085 – 1.945, p = 0.012) and mortality (HR = 1.010, 95%CI 1.003 – 1.017, p < 0.001) at 12 months, in the compensated patient group. The AUROC for AMM-ULN was 67.4% in 1-year decompensations and 69.5% in 1-year mortality, with similar results for ammonia levels. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months (p = 0.009 and p = 0.020, respectively).

Conclusion

Both ammonia levels and AMM-ULN were predictors of hepatic decompensation and liver-related mortality in compensated patients, at 12 months of follow-up. AMM-ULN ≥ 1.4 identified patients at higher risk of liver-related decompensation and mortality at 12 months.

References

D’Amico, G., Garcia-Tsao, G., & Pagliaro, L. (2006). Natural history and prognostic indicators of survival in cirrhosis: A systematic review of 118 studies. Journal of Hepatology, 44(1), 217–231. https://doi.org/10.1016/j.jhep.2005.10.013
Haj, M., & Rockey, D. C. (2018). Predictors of clinical outcomes in cirrhosis patients. Current Opinion in Gastroenterology, 34(4), 266–271. https://doi.org/10.1097/MOG.0000000000000450
De Franchis, R. et al (2022). Baveno VII – Renewing consensus in portal hypertension. Journal of Hepatology, 76(4), 959–974. https://doi.org/10.1016/j.jhep.2021.12.022
Shalimar, Sheikh, M. F. et al (2019). Prognostic Role of Ammonia in Patients With Cirrhosis. Hepatology, 70(3), 982–994. https://doi.org/10.1002/hep.30534
Tranah, T. H. et al (2022). Plasma ammonia levels predict hospitalisation with liver-related complications and mortality in clinically stable outpatients with cirrhosis. Journal of Hepatology, 77(6), 1554–1563. https://doi.org/10.1016/j.jhep.2022.07.014
Balcar, L. et al (2023). Impact of ammonia levels on outcome in clinically stable outpatients with advanced chronic liver disease. JHEP Reports, 5(4), 100682. https://doi.org/10.1016/j.jhepr.2023.100682
Elzeftawy, A. et al (2018). Evaluation of the blood ammonia level as a non-invasive predictor for the presence of esophageal varices and the risk of bleeding. The Turkish Journal of Gastroenterology. https://doi.org/10.5152/tjg.2018.17894