Could Commercial Formulations Replace Individualized Prescription in Pediatric Home Parenteral Nutrition?

OBJECTIVES: Standard parenteral nutrition (PN) solutions are safe and can meet the nutritional requirements of a significant number of pediatric patients. However, they may not always be adequate for those on long term PN. We aimed to compare the composition of individually tailored prescriptions in a pediatric population on home PN with that of available commercial PN formulations. METHODS: Retrospective analysis of the individual prescriptions of metabolically stable pediatric patients on home PN over a 1-year period (March 2019 to March 2020). These were compared with commercially available solutions with electrolytes, and replacement was considered adequate if three successive criteria were met: non-protein calorie to volume ratio (maximum variation 15%); non-protein calorie to nitrogen ratio (NPC:N) (maximum variation either 20% for long term use or 35% for possible short term use); electrolyte concentration (maximum increase 20%). RESULTS: Twenty-four patients were included (67% male; median age 7.5 years). The most common diagnosis was short bowel syndrome (58%). Replacement with a standard formulation was considered appropriate for possible short term use (maximum variation of 35% in NPC:N) in 16 (67%) patients and for long term use (maximum variation of 20% in NPC:N), the number of patients decreased to 10 (42%). CONCLUSIONS: Standard PN solutions can be adequate for a significant proportion of pediatric patients on home PN. Their use in the short term may also be appropriate in holiday periods or in settings of limited resources or restricted access to hospital facilities, such as those imposed by the COVID-19 pandemic.

Features of Fecal and Colon Microbiomes Associate With Responses to Biologic Therapies for Inflammatory Bowel Diseases: A Systematic Review.

BACKGROUND & AIMS: We performed a systematic review of changes in fecal and colon microbiomes of patients with inflammatory bowel diseases (IBDs) receiving treatment with monoclonal antibodies against tumor necrosis factor, integrins, or cytokines. We explored associations among microbiome composition and functions (at baseline and throughout the treatment) and therapy-related outcomes to determine whether colon or fecal microbiomes might be used as biomarkers of response to therapy. METHODS: We searched the PubMed, Web of Science, and Science Direct databases through February 2019 for studies of associations among the microbiomes of fecal or colon samples, biologic therapies, and IBDs. We used the critical appraisal skills program checklist to assess the quality of the study methods. RESULTS: From the 787 citations identified, 10 studies met the inclusion criteria. Changes in microbiomes of fecal or colon samples after treatment did not differ significantly among biologic agents; all produced decreases in relative abundances of Escherichia and Enterococcus and increases in genera that produce short-chain fatty acids. Fecal or colon microbiomes of patients who responded to therapy with antagonists of tumor necrosis factor or interleukins had higher α-diversity and increased relative abundances of different genera (Faecalibacterium, Roseburia, or Clostridium) from the Clostridiales order, either at baseline or during follow-up evaluation. Patients in remission after treatment with antibodies against integrins had decreased abundances of Roseburia. CONCLUSIONS: In a systematic review of 10 studies, we found evidence for consistent changes in microbiomes of fecal and colon samples from patients with IBD who responded to treatment with biologic agents. Prospective studies are needed to determine what changes are associated significantly with treatment, whether these changes are causes or effects of response, or whether the composition of the intestinal microbiome can be used to select treatments for patients with IBD.

Optimizing Antitumor Necrosis Factor Treatment in Pediatric Inflammatory Bowel Disease With Therapeutic Drug Monitoring.

Biological agents have revolutionized inflammatory bowel disease treatment but primary nonresponse and secondary loss of response are common with resulting adverse outcomes. Clinical trials demonstrated an association between serum drug concentrations, as well as the presence of antidrug antibodies, and loss-of-response. Therapeutic drug monitoring (TDM), defined as the evaluation of drug concentrations and antidrug antibodies, is appearing as a strategy to optimize treatment and take full advantage from these drugs. TDM appears to be a promising tool in clinical practice, especially in pediatric patients, who have pronounced fluctuations in the pharmacokinetics of the drugs.The authors present a literature review about antitumor necrosis factor therapy optimization based on personalized treatment strategies according to TDM and possible strategies to recapture loss of response, including an algorithm for practical management.

Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease.

BACKGROUND AND AIMS: The time course for the development of clinically significant hereditary diffuse gastric cancer (HDGC) is unpredictable. Little is known about the progression from preclinical, indolent lesions to widely invasive, aggressive phenotypes. Gastroendoscopy often fails to detect early lesions, and risk-reducing/prophylactic total gastrectomy (PTG) is the only curative approach. We present an HDGC family with early-onset disease in which clinical and histologic findings provided insight into the understanding of different HDGC phenotypes. METHODS: The proband was diagnosed at age 18 years with widely invasive, metastatic DGC. CDH1 genetic testing identified a pathogenic, germline CDH1 variant (c.1901C>T, p.Ala634Val). Thirty family members were tested, and 15 CDH1 carriers were identified. RESULTS: Six family members had PTG, with negative preoperative workup. The proband's 14-year-old sister is the youngest patient, reported to date, to have PTG after negative preoperative biopsy sampling. Intramucosal HDGC foci were detected in all PTG specimens (1-33). In contrast to the "indolent" phenotype of these foci, the aggressive DGC from the proband showed pleomorphic cells, absent E-cadherin expression, increased proliferation (Ki-67 index), and activation of oncogenic events (p53, pSrc and pStat3 overexpression). All family members had Helicobacter pylori gastritis. Cag-A-positive strains were detected in all specimens, except in the proband's sister. CONCLUSIONS: HDGC is a heterogeneous disease regarding clinical behavior, endoscopic findings, histopathologic features, and immunophenotypic/molecular profile. The presence of bizarre, pleomorphic cells in endoscopic biopsy specimens is suggestive of advanced disease and should prompt clinical intervention. The involvement of a full multidisciplinary team is essential for the management of these patients.

Gastric outlet obstruction in an 11-year-old girl: A case report.

Pyloric stenosis commonly affects infants and rarely causes gastric outlet obstruction in adolescents and older children. We present the case of an 11-year-old girl with a 2-month history of recurrent postprandial vomiting and weight loss. On physical examination, the patient presented with abdominal distension. Upper gastrointestinal endoscopy revealed a very small pyloric orifice through which the endoscope could not be advanced. Abdominal ultrasonography and a computed tomography confirmed pylorus thickening. She underwent Heineke-Mikulicz pyloroplasty with symptom resolution.

Peripheral inflammatory pseudotumor of the liver and extensive thrombosis of the portal venous system in a child.

We report a case of a peripheral inflammatory pseudotumor of the right lobe of the liver with extensive thrombosis of the portal venous system in a 9-year-old boy. Local thrombosis of the portal vein is a known complication of the inflammatory pseudotumor, especially in the hepatic hilum. The extent of the thrombosis in this case was unexpected, considering the peripheral location and the benign nature of the lesion. To our knowledge, thrombosis of this degree has not been described.

EVOLUTION OF DIAGNOSTIC DELAY IN PEDIATRIC INFLAMMATORY BOWEL DISEASE AND THE IMPACT OF THE COVID-19 PANDEMIC.

BACKGROUND: Pediatric inflammatory bowel disease (IBD) is increasingly prevalent, but diagnosis can still be challenging. Diagnostic delay is particularly deleterious in this age group. OBJECTIVE: This study explores the evolution of diagnostic delay in pediatric IBD and the influence of the COVID-19 pandemic. METHODS: Retrospective study including all pediatric IBD patients diagnosed during 2014, 2019 and 2020 in a tertiary hospital. Diagnostic delay, time to first medical visit, time to pediatric gastroenterologist (PG) visit and time to diagnosis were calculated and compared within a gap of five years (2019 and 2014) and with the year of onset of the pandemic (2020 and 2019). RESULTS: A total of 93 participants were included (2014: 32, 2019: 30, 2020: 31). No significant differences were observed in diagnostic delay, time to first medical visit in Crohn's disease (CD), time to PG visit and time to diagnosis when comparing 2019-2014 and 2020-2019. Time to first visit in ulcerative colitis (UC) and Undetermined-IBD increased in 2019 (P=0.03), with new decrease in 2020 (P=0.04). Diagnostic delay was longer in DC compared to UC plus Undetermined-IBD. CONCLUSION: Diagnostic delay is still an important matter in pediatric IBD, with no significant change over the last years. The time to the first PG visit and the time for diagnosis seem to have the greatest impact on diagnostic delay. Thus, strategies to enhance recognition of IBD symptoms among first-line physicians and to improve communication, facilitating referral, are of utmost importance. Despite the restraints in the health care system caused by the pandemic, time to diagnosis in pediatric IBD was not impaired during 2020 in our center.

Isotretinoin-Induced Distal Ileitis Mimicking Crohn's Disease.

Terminal ileitis is a common condition defined as inflammation of the terminal portion of the ileum, which is typically associated with inflammatory bowel disease (IBD), classically Crohn's disease (CD). However, it can have other etiologies, including drug-induced ones. Isotretinoin is an effective and commonly used treatment for acne vulgaris, presenting multiple adverse effects. There have been discussions over its association with enteric inflammation, particularly over IBD emergence risk. We report a case of a previously healthy 17-year-old female who presented transitory clinical, laboratory, imaging, and endoscopic evidence of distal ileitis, temporally related to extended isotretinoin treatment and mimicking CD. Repeated clinical, laboratory, imaging, and endoscopic reassessment after isotretinoin discontinuation confirmed an almost complete resolution of the condition, avoiding IBD misdiagnosis and specific medication initiation. Our case highlights the differential diagnosis of ileitis as being of critical importance to avoid further unnecessary diagnostic investigations and inadequate treatment. Serial re-evaluation may be of key importance to reach a final diagnosis. Although recent literature suggests that isotretinoin is not associated with an increased IBD risk, our case highlights the possibility of it inducing small bowel injury and inflammation, similar to what has been reported with other drugs.

Correction: Wilson's Disease: A Prevalence Study in a Portuguese Population.

[This corrects the article DOI: 10.7759/cureus.43718.].

Wilson's Disease: A Prevalence Study in a Portuguese Population.

Introduction Wilson's disease (WD) is a rare and underdiagnosed genetic disorder caused by anomalous tissue copper deposition, and for which epidemiological studies, specifically in Portugal, are scarce. Objectives This study aimed to evaluate the prevalence and incidence of WD and provide a description of its main clinical and laboratory features. Methods A retrospective study was carried out, with a search between 1995 and 2015, of all patients with a minimum follow-up of three months and birth confirmed in the northern region of Portugal, with an estimated population of 3,689,682 inhabitants. Database collection was based on the Portuguese National Health Service's clinical coding system, relying on clinical data from 13 northern Portuguese hospitals, liver biopsy histology results, and hospital prescription records. Clinical and biochemical correlations were statistically assessed using chi-square, Mann-Whitney U, Friedman, and Wilcoxon tests. Results Over the 20-year period, a prevalence of 1:37.000 and an incidence of one per million person-year was found. A total of 94 patients were analyzed, with a slight male predominance (53%), the majority with the onset of clinical manifestations in pediatric age (56%), with a median age at diagnosis of 16.6 years (interquartile range of 12.3-20,.8 years). Most patients presented with predominant liver disease (54.8%), with more than a third with cirrhosis; mixed hepatic and neurological manifestations in 17.9%; and mainly neurological symptoms in 10.7% of the patients. Neurological impairment was strongly associated with delayed development of the manifestations of the disease (p = 0.001) and also a higher detection of Kayser-Fleischer rings (p < 0.001), present in 27.0% of the patients. Regarding therapy, penicillamine has been the most widely used, with adverse reactions reported in 24.8%. At six and 12 months after initiation of therapy, a significant decrease in liver enzymes was found (ALT: p = 0.002; AST: p = 0.002, respectively), but no significant reduction was observed in urinary copper excretion. Conclusion This was one of the first studies regarding WD prevalence in a Portuguese population, contributing to a better understanding of the epidemiology, diagnosis, and management of WD in the northern region of Portugal. WD should be considered in any individual with unexplained hepatic or neurological manifestations, and initial symptoms may manifest at an early age, even in children less than five years old. A high percentage of patients were identified in the early stages of the disease by asymptomatic elevation of transaminases. Following copper chelation therapy, cytolysis markers appear to be more sensitive indicators of treatment response.

Serial transverse enteroplasty (STEP): intermediate outcomes in children with short bowel syndrome.

Short bowel syndrome is the most common cause of intestinal failure in children. The treatment is based on a multidisciplinary approach involving pediatricians, pediatric surgeons, and nutritionists. Surgical procedures for intestinal lengthening may be decisive, having been revalued after the recent description of serial transverse enteroplasty (STEP). We reviewed the patients who underwent the STEP operation for short bowel syndrome in our hospital in order to evaluate medium-term outcome. Between April 2006 and December 2008, three children were submitted to STEP without postoperative complications directly related to the procedure. In two cases the autonomy for oral/enteric feeding was obtained within 3 and 7 months after surgery with sustained growth, persisting at 5 years of follow-up after STEP. One child remained dependent of parenteral nutrition and was submitted to intestinal transplantation 30 months after STEP. However, since STEP until transplantation, it was possible to increase enteric volume and decrease intestinal dilation and the frequency of occlusive episodes. STEP is an effective and safe technique for intestinal lengthening that may allow increased tolerance to oral/enteric feeding or at least alleviate some complications of short bowel syndrome.

Poststeroid panniculitis: a rare complication of systemic corticosteroid therapy.

We report a 9-month-old male patient with autoimmune enteropathy treated with intravenous methylprednisolone who developed firm, red, subcutaneous nodules 20 days after abrupt steroid interruption. The diagnosis of poststeroid panniculitis (PSP) was made based on clinical and histological grounds. PSP is an unusual complication of systemic corticosteroid therapy, which might occur following rapid steroid tapering or withdrawal. Physicians should be aware of this rare condition and distinguish it from other causes of erythematous subcutaneous nodules and plaques in children.

Impact of COVID-19 in Pediatric Patients and Young Adults with Inflammatory Bowel Disease.

Introduction: Acute COVID-19 in pediatric and young adult patients tends to be milder in severity compared to adult infection. Recent studies seem to show that inflammatory bowel disease (IBD) patients are at no greater risk than the general population. We aim to describe our experience in the follow-up of pediatric and young adult patients with IBD followed in our center and determine possible risk factors of said population for severe COVID-19. Methods: We performed a retrospective study of all patients aged under 25 years followed for IBD at the Unit of Pediatric Gastroenterology in a tertiary center between December 2019 and April 2021 evaluating the incidence of COVID-19 and characterization of positive cases. Results: Of the 268 participants, 24 had COVID-19: the mean age was 19 years old and gender had an equal distribution; 75% (n = 18) had Crohn's disease, whereas only 25% (n = 6) had ulcerative colitis. Most patients were in clinical remission (n = 21). The majority of patients were under treatment with a tumor necrosis factor (TNF) antagonist (58%, n = 14), mainly infliximab, and most had no comorbidities other than IBD (83%). Regarding COVID-19, 17% of the patients were asymptomatic while the rest had only mild symptoms. There were no reported gastrointestinal complaints, no complications nor hospitalizations. Most patients did not require interruption of their IBD treatment. Conclusions: Our data suggest that pediatric and young adult IBD patients have a low risk for complications and hospitalization, regardless of IBD treatment. We believe that this experience is encouraging and allows for safe counseling regarding treatment options and school attendance in pediatric and young adult IBD patients.

Introdução: Na população pediátrica e de jovens adultos a gravidade da COVID-19 tende a ser moderada quando comparada com os doentes adultos. Os estudos mais recentes sugerem que os doentes com doença inflamatória intestinal (DII) não têm risco acrescido em relação à população geral. O objetivo do presente estudo é a descrição da nossa experiência no follow-up de crianças e jovens adultos com DII a COVID-19 e determinar a existência de possíveis fatores de risco para doença grave na referida população. Métodos: Foi realizado um estudo retrospetivo de todos os doentes com idade inferior a 25 anos, seguidos na Unidade de Gastrenterologia Pediátrico de um centro terciário por DII, com avaliação da incidência de COVID-19 entre dezembro de 2019 e abril de 2021, e caracterização dos casos postivos. Resultados: Entre os 268 participantes, 24 tiveram COVID-19. A idade média foi de 19 anos com uma distribuição por género equiparável. Destes, 75% (n = 18) tinham doença de Crohn, enquanto 25% (6) tinham colite ulcerosa. A maior parte dos doentes apresentavam-se em remissão clínica (n = 21) e, à data da doença COVID-19. A sua maioria, os doentes encontravam-se sob tratamento com antagonistas do fator de necrose tumoral (58%, n = 14), predominantemente o infliximab, e a generalidade dos doentes (83%) não apresentava outras comorbilidades além da DII. Relativamente à COVID-19, 17% eram assintomáticos enquanto os restantes apresentavam apenas sintomas ligeiros. Não houve relato de queixas gastrointestinais, complicações ou necessidade de hospitalização. Na maioria dos casos, não houve necessidade de interromper o tratamento da DII. Conclusão: Os nossos dados sugerem que doentes pediátricos e jovens adultos com DII apresentam um risco baixo de complicações ou hospitalização associados à COVID-19, independentemente do tratamento em curso para a DII. Este estudo apresenta resultados encorajadores e contribui para o aconselhamento adequado e fundamentado aos doentes e respetivos cuidadores, no que diz respeito às opções terapêuticas e frequência escolar dos doentes pediátricos e jovens adultos com DII.

Incidence Trends of Inflammatory Bowel Disease in a Southern European Country: A Mirror of the Western World?

INTRODUCTION: Inflammatory bowel disease (IBD) affects people from all age categories worldwide. Although the incidence of the disease is stabilizing or decreasing in most Western world countries, its prevalence is still increasing because of the rise in life expectancy and better disease management. This work intends to identify the trends related to IBD incidence nationwide, analyzing regional, sex, and age distributions. METHODS: Data were provided by the Portuguese Shared Services of the Ministry of Health. This study consisted of a retrospective analysis of all first consultations coded for "Chronic enteritis/ulcerative colitis" (D94) in a primary healthcare setting, between 2017 and 2020, in Portugal. The primary outcome measure was the IBD incidence rate per 100,000 inhabitants. We also calculated the incidence rate per person-year and forecasted incidence until 2024. RESULTS: Between 2017 and 2019, the incidence rate of IBD in Portugal decreased from 54.9 to 48.6 per 100,000 inhabitants. The average incidence was 20 new cases of IBD per 1,000 person-year. It was predicted that, in December 2023, IBD incidence would reach 305.4 new cases (95% Prediction Interval 156.6-454.3), a similar result to the values forecasted for December 2021 (305.4, 95% Prediction Interval 197.3-413.6). DISCUSSION: The incidence of IBD slightly declined from 2017 to 2019, and it is posed to stabilize in the future. The presented data are of the utmost importance for the characterization of IBD in Southern European countries and the establishment of future health policies in the setting of compounding prevalence in the Western world.