Children with intestinal failure need parenteral nutrition (PN) for long-term survival. PN-induced liver disease develops in 40% to 60% of infants who require long-term PN for intestinal failure (1). To our knowledge, rapid development of liver disease subsequent to PN has not been reported previously in children outside the neonatal period. We describe 2 children in whom liver disease developed within 45 days after the commencement of PN, secondary to an ischemic insult to the liver. CASE 1 A previously fit and well 2½-year-old boy was brought for medical attention with a short history of acute abdominal pain and vomiting. His condition deteriorated rapidly, and he needed cardiorespiratory resuscitation, including 2 doses of intravenous epinephrine. At laparotomy, a 360° volvulus with ischemic bowel from the duodenum to the middle of the transverse colon was identified. He underwent bowel resection and was left with less than 10 cm of small bowel. He showed biochemical evidence of acute renal tubular necrosis and ischemic hepatitis, with aspartate aminotransferase (AST) rising to 6406 IU/L and alanine aminotransferase (ALT) to 4237 IU/L within 48 hours. He required ionotropic support for 4 days. Other causes of abnormal liver function test results (LFTs) such as metabolic liver disease or drug-induced or viral hepatitis were excluded. The LFTs improved after day 5, returning to normal range by day 20. He was given PN through a central venous catheter 6 days after his initial presentation. The transaminases and total bilirubin (Fig. 1) began to increase steadily after 28 days. Bacterial central line infections developed on day 85 and day 151, and he was treated promptly with appropriate intravenous antibiotics. The enteral intake was restricted because of a high stoma output. He had no further line infections but experienced progressive liver dysfunction. In the context of ultra–short bowel syndrome and progressive liver disease, he was scheduled for liver and small bowel transplantation within 6 months of his initial presentation with an ischemic insult. He has recently undergone combined liver and small bowel transplantation.FIG. 1: Rising trend in ALT and bilirubin in case 1. ALT peaked to 4237 IU/L on day 5. A, PN commenced; B, venous catheter infections.CASE 2 A previously fit and well 3-month-old boy, born at term, was brought for medical attention with acute abdominal distension after an upper respiratory tract infection. Within 24 hours, his condition deteriorated, with respiratory failure requiring mechanical ventilation. He subsequently experienced a cardiac arrest and needed resuscitation for more than 10 minutes, including 3 doses of intravenous epinephrine. At laparotomy, he was found to have ischemic bowel, and 90 cm of bowel was resected. He needed ionotropic support for 13 days and hemofiltration for 15 days. He showed biochemical evidence of ischemic hepatitis, with AST rising to 1336 IU/L and ALT to 706 IU/L within 24 hours of the insult. The LFTs improved from day 2, returning to normal range by day 40. Other causes of abnormal LFTs such as metabolic liver disease or drug-induced or viral hepatitis were excluded. PN was commenced 5 days after his initial presentation. The transaminases along with the serum bilirubin began to increase steadily after 45 days. Catheter-related sepsis was treated 3 times (peak transaminases on day 96, day 154, and day 182) with appropriate intravenous antibiotics. A transient improvement in LFTs was noted each time. The enteral intake was initially restricted because of stricture-related intolerance to feeding. The infant experienced recurrent strictures requiring 6 laparotomies within 6 months. However, his LFTs continued to worsen, and he was referred for liver and bowel transplantation. At the last laparotomy, intestinal continuity was established, leaving a residual bowel length of 35 cm. After the last laparotomy, enteral feed tolerance improved, the LFTs continued to improve, and the infant was discharged to receive enteral feeding and home PN. At the 9-month follow-up his bilirubin was normal, and at the 15-month follow-up he had been weaned from PN to full enteral feeding. DISCUSSION Our cases illustrate the progression of liver disease in 2 infants with intestinal failure in the context of an ischemic injury to the liver. Ischemic hepatitis is rare because of the dual circulation (hepatic artery and portal vein) but is well documented in adults (2) and children (3) with shock and shows a characteristic pattern of LFTs. The AST and ALT rise within 24 hours of the ischemic insult and reach a peak exceeding >1000 IU/L. Plasma bilirubin and alkaline phosphatase concentrations are normal or only moderately elevated. When liver biopsy is performed, the pathological change is centrilobular necrosis. When the ischemic insult is immediately reversible, the usual trend is one of spontaneous recovery of the LFTs within 10 days (3). The development of liver disease after PN is usually gradual, has a multifactorial etiology, and has a wide clinical spectrum (1). The most important risk factors include prematurity, abdominal surgery in the neonatal period, recurrent episodes of sepsis (4) (including catheter infections), and lack of enteral feeding (1). Enteral feeding promotes bile flow, and thus attempts should be made to introduce it early. Our second case demonstrates the effect that enteral feeding can have in a child who could not tolerate early enteral feeding for mechanical reasons. It remains poorly understood, these factors notwithstanding, why PN-induced liver disease develops in some children at a relatively early stage compared with other children receiving PN. Jacquemain et al (5) reported a series of 18 premature infants receiving PN for necrotizing enterocolitis, of whom 9 showed evidence of cholestasis soon after PN was started. They concluded that shock and hypoxia, presumably involving a degree of hepatic ischemia, should be considered as an important risk factor for early PN-induced cholestasis. To our knowledge, a similar description of early PN-induced cholestasis in association with severe shock and ischemia has not been reported in children outside the neonatal period. The 2 patients described here had both experienced severe multiorgan failure, with ischemic liver injury that took longer than usual to resolve, and they went on to experience progressive liver disease within 45 days after PN was begun. Their trends in transaminases and bilirubin levels were almost identical, and in neither case was an alternative underlying liver disease found to explain the unusually rapid development of cholestasis, although catheter-related infections and lack of enteral feeding probably contributed. One child underwent liver and small bowel transplantation and is alive and well at the time of reporting. In the other child, with the progression of enteral feeding his liver disease stabilized. It is possible that a compromised cellular milieu at the time of institution of PN, such as that produced by severe ischemic insults, could be associated with more severe and progressive damage by PN, and this could be a rationale for delaying the start of PN until the LFTs show an improving trend (2,3,5). Indeed, experimental animal models have shown that hepatobiliary dysfunction can be seen as early as 5 days after total intravenous feeding is started (6). In summary, both children were extremely sick at the time of resuscitation, and their survival is possibly due to advances in pediatric intensive care. With greater access to expert resuscitation, more such patients are likely to be seen by clinicians. It remains a matter of clinical judgment when to start PN in children with evidence of acute liver injury, but these 2 cases provide a rationale for delaying PN. In conclusion, children who become dependent on PN as a result of a profound ischemic insult to the splanchnic circulation may have a higher risk of progression of liver disease. Acknowledgments The authors thank the intensive care units and nutritional care teams at Birmingham Children's Hospital and Alder Hey Children's Hospital and the community nursing teams based at the Countess of Chester Hospital for their assistance in the care of these children.
Wiley is a founding member of the UN-backed HINARI, AGORA, and OARE initiatives.They are now collectively known as Research4Life, making online scientifi c content available free or at nominal cost to researchers in developing countries.
Aliment Pharmacol Ther 2011; 34: 1282–1294 Summary Background Several published studies have evaluated the efficacy of tacrolimus in the management of Crohn’s disease with variable conclusions. Aim To review systematically the evidence examining the efficacy and safety of tacrolimus in treating Crohn’s disease. Methods The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PUBMED) and EMBASE (1984 to January 2011) were searched. Also, references from selected articles were examined. Case series (five or more patients), cohort and randomised controlled trials were eligible for inclusion, incorporating oral, intravenous or topical tacrolimus therapy. The primary outcome was induction of remission of active Crohn’s disease. Results Eleven studies met the inclusion criteria which included 163 patients, of which 127 received tacrolimus therapy. In patients with luminal Crohn’s disease, the crude pooled remission rate for tacrolimus was 44.3% (range, 7–69%) and the crude pooled response rate was 37.1% (range, 14–57%). For patients with perianal disease using systemic tacrolimus, crude pooled remission rate was 28.6% (range, 0–64%) and crude pooled response rate was 38.8% (range, 0–57%). Combining data from two studies using topical tacrolimus, 35.7% of patients achieved remission and 28.6% partial response. Nonserious adverse effects are common, particularly tremor, paraesthesia and headache. Reversible nephrotoxity occurred in 16% of patients. Conclusions The current evidence; although of a poor quality, appears to support the use of tacrolimus in Crohn’s disease. High quality randomised controlled trials are needed.
The fluorescein dilaurate test, a non-invasive test of exocrine pancreatic function, was carried out on 21 children with cystic fibrosis and pancreatic exocrine insufficiency, and 12 healthy siblings. The test clearly discriminated between the patients with cystic fibrosis and severe exocrine pancreatic insufficiency and the normal control subjects.
Summary Previously, we reported catch‐up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV 1 )‐, height‐, and sex‐matched comparison group receiving standard therapy. To evaluate long‐term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV 1 and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV 1 , p < 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short‐ and long‐term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study.
Quantum error correction with erasure qubits promises significant advantages over standard error correction due to favorable thresholds for erasure errors. To realize this advantage in practice requires a qubit for which nearly all errors are such erasure errors, and the ability to check for erasure errors without dephasing the qubit. We demonstrate that a “dual-rail qubit” consisting of a pair of resonantly coupled transmons can form a highly coherent erasure qubit, where transmon T1 errors are converted into erasure errors and residual dephasing is strongly suppressed, leading to millisecond-scale coherence within the qubit subspace. We show that single-qubit gates are limited primarily by erasure errors, with erasure probability perasure=2.19(2)×10−3 per gate while the residual errors are ∼40 times lower. We further demonstrate midcircuit detection of erasure errors while introducing <0.1% dephasing error per check. Finally, we show that the suppression of transmon noise allows this dual-rail qubit to preserve high coherence over a broad tunable operating range, offering an improved capacity to avoid frequency collisions. This work establishes transmon-based dual-rail qubits as an attractive building block for hardware-efficient quantum error correction. Published by the American Physical Society 2024
A healthy 15-year-old girl was referred to our Centre with two episodes of painless fresh rectal bleeding each lasting for a few days. The blood was not mixed with stool. Stools were described as normal and there was no recent change in her bowel habits. There was no abdominal pain or other symptoms referable to the GI tract. Her father had a similar problem that he attributed to hemorrhoids. Physical examination was normal. She had routine investigations including complete blood count, blood urea nitrogen and serum electrolytes, liver function tests and inflammatory markers. All were within normal values. Colonoscopy was performed and biopsies taken. The histopathology of transverse colonic biopsy is shown in (Fig. 1).FIG. 1: Transverse colonic biopsy histopathology.What is the diagnosis? Ulcerative colitis. Rectal polyp. Enterobius vermicularis infestation. Meckel's diverticulum. ANSWER C. Enterobius vermicularis (Threadworm) Infestation. Figure 2 shows a segment of colonic mucosa. The surface epithelium is intact with mild patchy mucus-cell depletion. The lamina propria is edematous with a moderate increase in chronic inflammatory cells, especially eosinophils. One E. vermicularis worm is present (Fig. 2, arrow). The patient was treated with a single dose of albendazole that was repeated after 2 months. The patient made a full recovery with no further rectal bleeding.FIG. 2A: segment of colonic mucosa. One Enterobius vermicularis worm is present (arrow).Enterobius vermicularis is a nematode with worldwide distribution, although it is most prevalent in temperate and cold climates. Children are most often infected, but infestation can spread rapidly among family members. Infection spreads by direct transmission of ova from person to person or indirectly on clothing or house dust (1). Although nocturnal anal pruritus is usually the most common presenting symptom, there have been a few reports of E. vermicularis-induced eosinophilic colitis presenting with bloody diarrhea (2,3). Ova can be detected in the perianal region by applying a clear adhesive tape to the perianal skin and examining this microscopically. A single oral dose of albendazole is the treatment of choice, although pyrantel pamoate and piperazine are also effective. Treatment of the entire family is usually indicated (4). A second dose might be needed, as re-infestation can occur as early as 2 months after initial treatment (1).
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