bluuebunny/crossref_metadata_2025 huggingface dataset:
Sweat Test Results in Children with Primary Protein Energy Malnutrition
Authors: Yiğit Hakan , Selimoğlu Mukadder Ayşe , Altinkaynak Sevin
Published: January 2024

Objectives

In underdeveloped and developing countries where protein energy malnutrition (PEM) is common, it is sometimes difficult to exclude the diagnosis of cystic fibrosis (CF) in malnourished children because both primary PEM and CF share similar symptoms, signs, and laboratory findings, such as elevated sweat chloride value. This study was performed to investigate sweat test results and determine percentile values in children with primary PEM.

Methods

A total of 90 children with PEM and 30 healthy children were included. PEM was classified according to criteria defined by Gomez, Waterlow, and McLaren. Sweat tests were performed using the Macroduct conductivity system.

Results

Patient age and gender did not affect the test results (P > 0.05). The mean sweat conductivity (equivalent NaCl mMol/L) of patients with PEM was higher than that of controls (P < 0.001) and increased with the degree of malnutrition (P < 0.001). Inverse correlations between sweat conductivity and weight for age, height for age, and weight for height were detected (P < 0.001). The highest value was found in children with wasting and stunting, followed by those with stunting (P < 0.05) and those with marasmic kwashiorkor (P < 0.01). Of all children with PEM, 6.7% had elevated sweat test results that normalized after nutritional management; of children with third degree PEM, the figure was 20%. Ninety‐fifth percentile values of first, second, and third degree malnutrition were 47 mMol/L, 49 mMol/L, and 69 mMol/L, respectively.

Conclusion

Elevated sweat test result is not an important problem, especially in first and second degree PEM, but borderline values can be detected in as many as 20% of cases of third degree malnutrition. Sweat conductivity may increase to 69 mMol/L in children with stunting, those with wasting and stunting, and in those with third degree PEM.
The Effect of Early Treatment in Children with Chronic Hepatitis
Authors: Hartman Corina , Berkowitz Drora , Rimon Nurit , Shamir Raanan
Published: January 2024

Background

The aim of this study was to compare the efficacy of interferon alpha (IFN) or IFN and ribavirin (IFN+RIB) combination therapy in children with chronic hepatitis C (CHC). Most children were infected during treatment for pediatric malignancies.

Patients and Methods

We reviewed the charts of 20 patients (11 boys and 9 girls) aged 10.6 ± 3.7 years with CHC who were treated between 1995 and 2001. Seven patients diagnosed with CHC before 1998 were treated with 3 million units of IFN three times weekly for 6 to 12 months. Thirteen children diagnosed after 1998 were treated with 3 million units of IFN three times weekly plus 15 mg/kg of ribavirin daily for 6 months (IFN+RIB).

Results

Demographic and clinical characteristics were not different between the two treatment groups. A sustained complete response defined as serum alanine aminotransferase normalization and hepatitis C virus RNA clearance at 6 and 12 months after termination of treatment occurred in three of seven children (43%) treated with IFN monotherapy compared with 7 of 12 children (54%) in the group treated with IFN+RIB combination therapy (not significant). The only difference between responders and nonresponders was the duration of infection before the initiation of therapy, which was significantly shorter in responders (1 ± 0.3 vs. 5.6 ± 2.2; P = 0.001).

Conclusions

In this small cohort of children with CHC, early initiation of antiviral treatment was associated with a sustained response rate independent of treatment type. Regular follow‐up of children at risk of acquiring hepatitis C virus infection should assist in the early diagnosis. Early initiation of antiviral treatment may improve the rate of sustained response.
Immunogenicity and Safety of Hepatitis A Vaccine in Children With Chronic Liver Disease
Authors: Ferreira Cristina Targa , da Silveira Themis Reverbel , Vieira Sandra Maria , Taniguchi Adriano , Pereira‐Lima Jorge
Published: January 2024

Background

Acute hepatitis A superimposed on chronic liver disease has been associated with a more severe course of disease and development of fulminant hepatitis. The aim of this study was to evaluate the immunogenicity and safety of an inactivated hepatitis A virus vaccine in children with chronic liver disease.

Patients and Methods

This was an open, prospective, and controlled trial with 89 anti‐HAV negative children between 1 and 16 years of age studied at a pediatric liver disease and transplantation referral center. Inactivated HAV vaccine (Havrix), from GlaxoSmithKline Biologicals containing 720 Elisa units of alum‐adsorbed hepatitis A antigen per 0.5 ml dose was used. Thirty‐four pediatric patients with chronic liver disease (mean age: 7.0 ± 4.86 years) and 55 healthy controls (mean age: 4.8 ± 2.7 years) received two doses of Havrix vaccine in months zero and six. Seroconversion and anti‐HAV titers expressed as geometric mean titers (GMT) in mIU/ml were measured at months one and seven, by a modified Hepatitis A virus andibodies (HAVAB) assay.

Results

Seroconversion rates at four weeks after primary immunization were 76% and 94% and the GMT 107.77 and 160.77 mIU/ml in the patient and control groups, respectively. One month after second dose the seroconversion rates were 97% and 100% in the groups with GMT of 812.40 and 2344.90 mIU/ml. Both doses were well tolerated with no significant adverse events observed. Local injection‐site symptoms were the most common reactions reported in both groups.

Conclusion

Although GMTs were significantly lower in children with chronic liver disease compared to healthy controls, the overall seroconversion rates were not different. Hepatitis A virus vaccine was safe, well‐tolerated, and immunogenic in children with chronic liver disease.
Recombinant Factor VIIa Improves Coagulopathy Caused by Liver Failure
Authors: Brown Jeffrey B. , Emerick Karan M. , Brown Deborah L. , Whitington Peter F. , Alonso Estella M.
Published: January 2024

Objective

Coagulopathy is an important cause of morbidity and mortality in patients with liver failure. The benefit of traditional therapies to correct coagulation is often limited and short‐lived. Our aim is to identify indications for rFVIIa use and the outcome of treatment in children with liver failure.

Methods

A retrospective review from July 2000 to December 2001 was performed to identify consecutive patients with acute or chronic liver failure who received rFVIIa. Prothrombin times (PT) before and after therapy were compared by paired t test.

Results

Fifteen patients were treated with rFVIIa for coagulopathy caused by liver failure. All were receiving fresh frozen plasma (mean infusion rate, 39.7 mL/kg/day) when rFVIIa therapy was started. The mean PT before rFVIIa was 32.0 ± 7.0 seconds. One hour after infusion, the PT normalized to 13.7 ± 2.4 seconds (P < 0.0001) and remained significantly reduced at 6 hours (19.8 ± 5.3 seconds; P < 0.0001). A sustained improvement was maintained during the subsequent 3 days. Five of seven patients with bleeding complications improved clinically after rFVIIa treatment. Two of the bleeding patients also benefited from improved fluid balance as fresh frozen plasma support was reduced. No thrombotic events were attributed to rFVIIa therapy.

Conclusions

In patients with liver failure, rFVIIa therapy quickly normalizes the PT and maintains improved hemostasis, even when coagulopathy has been refractory to fresh frozen plasma. Therapy subjectively reduces clinical bleeding and can improve fluid balance, without complications.
Cytokines, Chemokine Receptors, and Homing Molecule Distribution in the Rectum and Stomach of Pediatric Patients with Ulcerative Colitis
Authors: Berrebi D. , Languepin J. , Ferkdadji L. , Foussat A. , De Lagausie P. , Paris R. , Emilie D. , Mougenot J. F. , Cezard J. P. , Navarro J. , Peuchmaur M.
Published: January 2024

Background

Cytokines appear to play a significant role in the pathogenesis of inflammatory bowel disease (IBD) with a predominant Th2 pattern in colonic mucosa of patients with ulcerative colitis (UC). Chemokines and their receptors also regulate the migration of Th1 or Th2 lymphocytes to inflammatory tissues during the immune response. Although adult UC is usually confined to the colon, pediatric UC not uncommonly affects the stomach.

Aims

The aim of this study was to compare expression of cytokines, chemokine receptors, and homing molecules in the rectal and the histologically characterized gastric mucosa of pediatric patients with UC.

Subjects

Sixteen patients (11 girls and 5 boys; median age, 9 years) having all the features of UC were included in the study.

Methods

Rectal and gastric mucosa obtained from UC cases were immunostained with antibodies against L‐selectin, β7 integrin, CXCR3, CCR3, and CCR5. IL‐4 and IL‐12 p40 transcript expression was studied by in situ hybridization.

Results

Chronic gastritis was found in 93.7% of cases and Helicobacter pylori (Hp) was found in 2 (13.3%) cases. In the rectal and gastric mucosa, CXCR3 was found in perivascular lymphocytes and CCR5 in a subset of CXCR3+ cells in the lamina propria. CCR3+ lymphocytes and IL‐4–positive cells were always found, but there was no evidence of IL‐12 production. Most of the lymphocytes infiltrating the gastric mucosa expressed β7 but not CD62L. In contrast, β7‐positive cells were randomly dispersed in the rectal lamina propria, and the fraction of CD3+β7+ was low.

Conclusions

The authors conclude that gastritis is common in pediatric UC. The presence of CCR3+ lymphocytes, IL‐4 transcript expression, without IL‐12 p40 production in the stomach and in the rectum suggests a Th2 immune response. The presence of CCR3+, CD62L‐ activated Th2 cells may suggest that these gastric cells are recruited from colorectal primary lesions.
Internal Anal Sphincter Achalasia in Children: Clinical Characteristics and Treatment with Clostridium botulinum Toxin
Authors: Ciamarra Paola , Nurko Samuel , Barksdale Edward , Fishman Steven , Di Lorenzo Carlo
Published: January 2024

Objectives

To describe the clinical characteristics of children with internal anal sphincter (IAS) achalasia and to evaluate the benefit of intrasphincteric injection of Clostridium botulinum toxin.

Methods

Retrospective review of the medical records of 20 patients (8 male, mean 5.8 ± 4.2 years) with severe chronic constipation and IAS achalasia. Each patient received four‐quadrant, intrasphincteric injections of botulinum toxin at a dose of 15–25U per quadrant. Patients were reassessed 4 weeks‐18 months after injection. We compared the clinical characteristics of these patients to 20 consecutive children (14 male, mean age 8.1 + 4.6 y) with functional constipation (control group).

Results

The children with IAS achalasia had earlier onset of symptoms, less fecal soiling, and less withholding behavior than the control children. Response to botulinum injection was rated excellent by the parents in 60% and by the physician in 35% of children. There was wide individual variability in the frequency of defecation after therapy. Duration of response ranged from 1 week to 18 months.

Conclusions

Children with IAS achalasia have clinical characteristics differentiating them from children with functional constipation. Intra‐anal injection of botulinum toxin is a safe and effective short‐term treatment for these children.
A Multicomponent Behavioral Program for Oral Aversion in Children Dependent on Gastrostomy Feedings
Authors: Byars Kelly C. , Burklow Kathleen A. , Ferguson Kathleen , O'Flaherty Therese , Santoro Kathy , Kaul Ajay
Published: January 2024

Objectives

Describe outcomes in nine children with Nissen fundoplication and feeding gastrostomy treated in a multicomponent feeding program. The importance of comprehensive evaluation, appetite regulation, and family‐focused intervention within a behavioral feeding program are discussed.

Methods

Prospective clinical intervention with dependent measures evaluated before treatment, after treatment, and at follow‐up.

Results

Nine children (4 girls; mean age, 3.1 ± 1.2 years; range, 1.8–5.5 years) and their mothers were admitted for intensive treatment (mean duration, 11.4 ± 1.7 days; range, 5–16 days). At discharge, 4 of 9 (44%) children were weaned completely from gastrostomy feedings. The mean oral intake of all patients increased 50% from pretreatment to posttreatment assessment. At a mean of 3.1 ± 0.5 months (range, 2.4–3.6 months) after treatment, six of nine children were weaned completely from gastrostomy feedings. The percent of daily nutritional needs consumed orally increased from a pretreatment mean of 14.6% ± 21.2% (range, 0%–67%) to a posttreatment mean of 63.4% ± 18.3% (range, 34%–85%) and a follow‐up mean of 88.1% ± 25.1% (range, 30%–100%). The mean percent ideal body weight for height was not compromised during intensive treatment.

Conclusions

Short‐term intensive biobehavioral treatment was successful in improving oral intake and weaning from gastrostomy tube feeding in children with Nissen fundoplication and feeding gastrostomy.
Age and Family History at Presentation of Pediatric Inflammatory Bowel Disease
Authors: Weinstein Toba A. , Levine Mindy , Pettei Michael J. , Gold David M. , Kessler Bradley H. , Levine Jeremiah J.
Published: January 2024

Objectives

Young children are thought to be a unique subset of pediatric patients with inflammatory bowel disease (IBD). The authors' objective was to evaluate the differences in initial clinical presentation of young and older children with IBD and to determine whether a positive family history of IBD is associated with the age of presentation.

Methods

The authors reviewed the records of all patients with new diagnoses of Crohn disease (CD) and ulcerative colitis (UC) who presented between July 1996 and July 1999. Initial evaluation included assessment of growth parameters and laboratory values (hemoglobin concentration, platelet count, erythrocyte sedimentation rate, and serum albumin). Inquiry regarding a family history of IBD was made in every patient.

Results

There were 153 patients with new diagnoses (82 with CD and 71 with UC), with a mean age of 11.9 years (range, 16 months–18 years). The children with CD had a higher sedimentation rate and platelet count and a lower mean hemoglobin concentration and serum albumin at presentation than did children with UC. Body mass index (BMI) was significantly lower in patients with newly diagnosed CD than in those with UC. The only significant laboratory differences between patients younger than 11 years and those 11 years or older was a higher mean platelet count in patients with CD who were younger than 11 years. Of the younger patients with CD, 41.7% had a positive family history of IBD, which was significantly greater that that found in the older patients with CD.

Conclusions

Except for higher platelet counts, a lower BMI, and a higher frequency of positive family history in young children with CD, there were no significant differences in the presentation of young children with IBD compared with older children.
Impact of Helicobacter pylori Infection on Growth of Children: A Prospective Cohort Study
Authors: Bravo Luis Eduardo , Mera Robertino , Reina Julio Cesar , Pradilla Alberto , Alzate Alberto , Fontham Elizabeth , Correa Pelayo
Published: January 2024

Objective

The aim of this study was to prospectively follow a cohort of children without Helicobacter pylori infection and to compare growth velocity in the children who become infected during follow‐up with that of children who remained infection‐free.

Methods

Three hundred forty‐seven children in general good health, aged 12 to 60 months, who tested negative for H. pylori by the 13C‐urea breath test, from three daycare centers in a lower‐middle class borough of Cali, Colombia, were monitored for 2.5 years. Anthropometric measurements were performed every 2 months and breath tests every 4 months. Linear mixed models were used to analyze growth velocity in relation to onset of H. pylori infection.

Results

One hundred five (30.3%) children who were uninfected at the start of the study became infected during follow‐up. Growth velocity in infected children was reduced by 0.042 ± 0.014 cm/mo (P = 0.003) (approximately 0.5 cm/yr) after adjusting for age. The rate of deceleration in growth velocity was relatively constant over time.

Conclusions

Among these lower‐middle class children aged 12 to 60 months from a population with high prevalence of H. pylori infection, a new and sustained infection was followed by significant growth retardation.
Outcomes of Pediatric Gastroesophageal Reflux Disease: In the First Year of Life, in Childhood, and in Adults . . . Oh, and Should We Really Leave Helicobacter pylori Alone?
Authors: Gold Benjamin D.
Published: January 2024

The prevalence of gastroesophageal reflux (GER) in childhood varies by age. As in adults, GER can result in a spectrum of disease manifestations. Children with gastroesophageal reflux disease (GERD) may become adults with GERD, as suggested by the frequency of childhood reflux symptoms reported by adults with reflux disease. Some studies suggest a causative association between Helicobacter pylori infection and GERD, whereas others postulate a protective role for H. pylori. To better understand pediatric GERD, age‐appropriate case definitions and multicenter randomized controlled treatment trials are critically needed.
Zinc With Oral Rehydration Therapy Reduces Stool Output and Duration of Diarrhea in Hospitalized Children: A Randomized Controlled Trial
Authors: Bhatnagar Shinjini , Bahl Rajiv , Sharma Punit K. , Kumar Geeta T. , Saxena S. K. , Bhan Maharaj K.
Published: January 2024

Objectives

The authors evaluated the effect of zinc treatment as an adjunct to oral rehydration therapy on stool output and diarrheal duration in children with acute noncholera diarrhea with dehydration.

Methods

This double‐blind, randomized, controlled trial was conducted at two urban hospitals in New Delhi. A total of 287 dehydrated male patients, ages 3 to 36 months, with diarrhea for ≤ 72 hours were enrolled. They were assigned to zinc or placebo by a randomization scheme stratified by age (≤ or >12 months) and weight for height (65%–80% or >80% National Centre for Health Statistics median). Participants in the zinc group received 15 mg (≤12 months) or 30 mg (>12 months) elemental zinc daily in three divided doses for 14 days. The main outcome measures were stool output and diarrheal duration.

Results

Zinc treatment reduced total stool output (ratio of geometric means, 0.69; 95% confidence interval [CI]: 0.48, 0.99) and stool output per day of diarrhea (ratio of geometric means, 0.76; 95% CI: 0.59, 0.98). The risk of continued diarrhea was lower (relative hazards, 0.76; 95% CI: 0.59, 0.97) and the proportion of diarrheal episodes lasting ≥ 5 days (odds ratio, 0.49; 95% CI: 0.25, 0.97) or ≥ 7 days was less (odds ratio, 0.09; 95% CI: 0.01, 0.73) in the zinc group.

Conclusions

This study demonstrates a beneficial effect of zinc administered during acute diarrhea on stool output, diarrheal duration, and proportion of episodes lasting more than 7 days. The effects are large enough to merit routine use of zinc during acute diarrhea in developing countries.
Colostomy for Treatment of Functional Constipation in Children: A Preliminary Report
Authors: Woodward Mark N. , Foley Peter , Cusick Eleri L.
Published: January 2024

Objectives

Surgery is indicated in very few children with intractable functional constipation. A number of operations have been described with unpredictable outcome and significant morbidity. The authors present a series of 10 children who underwent a Hartmann procedure with end colostomy formation.

Method

Preoperative management, in addition to maximum conservative measures, included psychologic referral, rectal biopsy, transit studies, and contrast enemas. A standard Hartmann procedure was performed with on‐table rectal washout, formation of a proximal sigmoid colostomy, limited anterior resection of hypertrophic proximal rectosigmoid, and oversewing of the rectal stump.

Results

The series includes 10 pediatric patients (4 female, 6 male), in whom constipation was first reported at a median age of 3 years (range, 2 months–7 years) and surgical referral was made at 8 years (range, 1–14 years). Surgery was performed at a median age of 9.5 years (range, 2–15 years), and the median postoperative stay was 5 days (range, 4–9 days). Complications occurred in four patients (transient mild rectal discharge in 2, stomal prolapse in 1, and an unrelated small bowel obstruction in 1 patient with an additional Mitrofanoff stoma). Median postoperative follow‐up was 31 months (range, 9–56 months), and the children and parents were all completely satisfied with the stoma.

Conclusion

Colostomy formation is a potential surgical option for severe functional constipation with low associated morbidity and high patient satisfaction.
Infliximab in Pediatric Ulcerative Colitis: Two‐year Follow‐up
Authors: Mamula Petar , Markowitz Jonathan E. , Cohen Louis J. , von Allmen Daniel , Baldassano Robert N.
Published: January 2024

Objectives

The role of infliximab in treating pediatric ulcerative colitis (UC) is not defined. The authors previously have described their experience with the open label use of infliximab in nine children with moderate to severe UC. The aim of this study was to describe the outcome of these patients after a minimum 2‐year follow‐up and to describe the responses of eight additional patients to this medication.

Methods

The authors reviewed all pediatric patients with UC who received infliximab at The Children's Hospital of Philadelphia from its first use until February 2003. Tolerance of the infusions and adverse events were recorded.

Results

Follow‐up information for a minimum of 2 years was reviewed for the nine initial patients. A total of 73 infliximab infusions were administered to these patients. Seven of nine (78%) patients were considered to be responders to the initial dose of infliximab. Two of these patients became nonresponders within 9 months of the first dose of infliximab and underwent colectomy. Of the remaining five (56%) patients with sustained response, two continue to receive infliximab infusions and three are doing well without infliximab. One patient experienced an infusion reaction, and one experienced herpes zoster infection. We have treated eight additional UC patients with infliximab. Seven (88%) patients were considered responders. One responder experienced relapse within 2 months. Overall, a short‐term improvement was seen in 14 of 17 (82%) patients, and sustained improvement in 10 of 16 (63%) patients followed up for more than 9 months. All five patients with severe or fulminant UC, unresponsive to 2 weeks of intravenous corticosteroid therapy, experienced improvement with infliximab. Infliximab was well tolerated.

Conclusion

Infliximab is associated with short‐ and long‐term clinical improvement in children and adolescents with moderate to severe UC.
Duodenogastric Bile Reflux Is Common in Cystic Fibrosis
Authors: Hallberg K. , Fändriks L. , Strandvik B.
Published: January 2024

Background

Patients with cystic fibrosis (CF) have a high incidence of gastroesophageal reflux disease, but few cases of mucosal injury are reported. Duodenogastric reflux has not been studied in CF but has been suggested to have a pathogenic role in producing alkaline injury to the esophageal mucosa. The aim of this study was to analyze the presence of duodenogastric reflux in patients with CF.

Patients and Methods

Ten patients with CF and 7 healthy volunteers participated in the study. Gastroduodenal manometry and intragastric perfusion were performed in all subjects. Gastric perfusate was analyzed for bilirubin and bile acids. Only patients and controls exhibiting normal migrating motor complexes were evaluated.

Results

Eight patients with CF had normal motility recordings and had significantly higher gastric bilirubin levels compared with healthy subjects (P = 0.003). The bilirubin concentration was associated with bile acid regurgitation in five patients with CF. All bile acids were conjugated with a high glycine/taurine ratio and low levels of secondary bile acids. Small amounts of keto bile acids were found in two patients.

Conclusion

The patients with CF had an increased incidence of duodenogastric reflux compared with healthy subjects. The bile acid composition was typical for CF with low levels of secondary bile acids. Although high bile acid concentration was found in the duodenogastric reflux in most patients with CF, the less toxic profile of the bile acids might possibly contribute to the low frequency of Barrett's esophagus in CF.
Bone Mineral Density and Bone Acquisition in Children and Young Adults with Cystic Fibrosis: A Follow‐up Study
Authors: Ujhelyi Rita , Treszl András , Vásárhelyi Barna , Holics Klára , Tóth Miklós , Arató András , Tulassay Tivadar , Tulassay Zsolt , Szathmári Miklós
Published: January 2024

Objective:

To investigate bone mineral density and bone homeostasis in cystic fibrosis (CF) and to assess changes in a 2‐year period.

Methods:

Thirty‐eight patients with clinically stable CF (11 children, 16 adolescents, 11 young adults) were enrolled. No patient was treated with corticosteroids before or during the study. Weight and height Z scores and bone mineral density (BMD) Z‐score at the femoral neck and the lumbar spine were recorded at the beginning of the study and after 2 years. Osteocalcin and cross‐link excretion, both measurements of bone turnover were also measured. Correlations between BMD, bone turnover parameters, disease severity, pubertal stage, and nutritional state were calculated. The maternal BMD was also determined and related to that of the child.

Results:

Height and weight Z scores were normal in children and below normal in adolescents. Puberty was delayed in most patients. Bone age was lower than chronological age in adolescents. Lumbar spine and femoral neck BMD Z scores were below normal in each age group. Disease severity determined by Schwachman score correlated with lumbar BMD (r = 0.45, P < 0.02). BMD Z scores did not change during 2 year follow‐up. Maternal and patient lumbar and femoral BMD correlated significantly (r = 0.51, P < 0.01, and r = 0.54, P < 0.01, respectively).

Conclusions:

Bone deficit is present in patients with CF who have never received steroid treatment. Delay of puberty, chronic inflammation, or genetic susceptibility might be responsible for this phenomenon which was found in patients who had never received steroids and who were in relatively good clinical state.
Effect of Locust Bean Gum in Anti‐regurgitant Milk on the Regurgitation in Uncomplicated Gastroesophageal Reflux
Authors: Miyazawa Reiko , Tomomasa Takeshi , Kaneko Hiroaki , Morikawa Akihiro
Published: January 2024

Objectives:

To evaluate the efficacy of anti‐regurgitant milk (AR milk) with reduced concentration of locust bean gum (LBG) compared with the usual commercially available concentration of this thickener.

Methods:

Thirty infants with daily regurgitation but no other medical problems were randomly assigned to one of two groups. Infants in group A (n = 16) were fed either HL‐450, an AR milk thickened with a commonly used concentration of LBG (0.45 g/100 mL) or control milk (HL‐00; no LBG) in a crossover manner for periods of 1 week. The order of milk was randomly chosen for each subject. Infants in group B (n = 14) were fed HL‐350, an AR milk with a reduced LBG concentration (0.35 g/100 mL), or HL‐00 in the same crossover fashion. The number of episodes of regurgitation, feeding time, and body weight gain were recorded. Three infants in group B did not complete the protocol and were excluded.

Results:

Both AR formulas decreased the number of regurgitation episodes by approximately 50% compared with control. Five mothers who gave their infants HL‐450 and no mothers who fed their children HL‐350 reported that the infants had difficulty sucking the formula through the nipple. Thirteen (81.3%) mothers who used HL‐450 and 9 (81.8%) mothers who used HL‐350 preferred the AR milk to the control milk.

Conclusions:

An AR milk with reduced LBG was as effective in reducing regurgitation as one with the usually available concentration of LBG.
Helicobacter pylori and Peptic Ulcer: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
Authors: Drumm Brendan , Day Andrew S. , Gold Ben , Gottrand Frederic , Kato Seiichi , Kawakami Elisabete , Madrazo Armando , Snyder John , Thomas Julian
Published: January 2024

Research

Determine the age of acquisition of H. pylori infection in diverse populations and the mode of transmission.

Intervention

Validate noninvasive methods for determining H. pylori colonisation in childhood.

Education

Train physicians to identify early indicators of long‐term morbidity (i.e., gastric cancer).
Inflammatory Bowel Disease: Working Group Report of the Second World Congress of Pediatric Gastroenterology, Hepatology, and Nutrition
Authors: Murch Simon H. , Baldassano Robert , Buller Hans , Chin Simon , Griffiths Anne M. , Hildebrand Hans , Jasinsky Clara , Kong Tse , Moore David , Orsi Marina
Published: January 2024

Research

Determine the genotype‐phenotype correlation for different patient groups.

Determine whether mucosal responses in IBD differ between children and adults.

Determine the role of infectious exposures in paediatric IBD.

Intervention

Determine whether early aggressive therapy can alter the natural history of IBD.

Facilitate the rapid assessment of novel agents in paediatric practice by establishing an international paediatric IBD clinical trials bureau.

Determine the factors that improve quality of life.

Education

Determine the global epidemiology of IBD and its environmental triggers.

Establishment of IBD databases for initial presentation and follow‐up data.

Identify the factors that lead to optimal delivery of high‐quality care.
Nutrition Support for Pediatric Patients With Inflammatory Bowel Disease: A Clinical Report of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition
Authors: Kleinman Ronald E. , Baldassano Robert N. , Caplan Arlene , Griffiths Anne M. , Heyman Melvin B. , Issenman Robert M. , Lake Alan M.
Published: January 2024

Impairment of growth and malnutrition are significant complications of inflammatory bowel disease (IBD) in pediatric patients. Since this topic was last reviewed in these pages (1), a number of studies have further explored the epidemiology and pathogenesis of these nutritional complications of IBD in an effort to provide more effective interventions to prevent the long‐term consequences of chronic nutrient deficiencies in childhood. In addition, during the past 15 years, the use of selected nutrients and microorganisms (probiotics) as primary or adjunctive therapy for the treatment of IBD has become an emerging area of great interest. The following is a Clinical Report from the Nutrition and Inflammatory Bowel Disease Committees of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.
Dietary Nucleotides and Intestinal Blood Flow Velocity in Term Infants
Authors: Carver Jane D. , Sosa Roberto , Saste Monisha , Kuchan Matthew
Published: January 2024

Objectives:

Two previous studies have shown that the addition of nucleotides to single feedings of formula is associated with increased 90‐minute postprandial superior mesenteric artery (SMA) blood flow velocity (BFV). To assess the effect of chronic feeding of nucleotide‐supplemented formula, we measured pre‐ and postprandial SMA BFV in term infants fed formula with or without added nucleotides for 4 weeks.

Methods:

At 1 week of age, healthy, term infants were randomized to receive formula with added nucleotides (NT+), or formula without added nucleotides (NT−) from age 1 to 5 weeks. When the infants were 5 weeks of age, SMA BFV was measured by Doppler ultrasound 15 minutes before the assigned feeding (baseline) and 30, 60, and 90 minutes after the start of feeding. A reference group of human milk‐fed infants was studied before and after breast feeding.

Results:

Thirty formula‐fed (NT+ = 17; NT− = 13) and 10 human milk‐fed infants were studied. Baseline BFV was similar among the three groups. BFV increased in each group from baseline to 30 minutes after initiation of feeding and progressively declined from 30 to 90 minutes in infants fed NT− formula or human milk. In infants fed NT+ formula, BFV decreased between 30 and 60 minutes. However, from 60 to 90 minutes, velocity was unchanged or increased. At 90 minutes, mean and peak systolic velocities were significantly greater in the NT+ group than the NT− group (P < 0.001).

Conclusions:

These data agree with those of previous studies showing increased 90‐minute postprandial SMA BFV after a feeding with nucleotide‐supplemented formula. The clinical significance of these findings is unknown.
Infliximab Therapy in 30 Patients With Refractory Pediatric Crohn Disease With and Without Fistulas in The Netherlands
Authors: de Ridder Lissy , Escher Johanna C. , Bouquet Jan , Schweizer Joachim J. , Rings Edmond H. H. M. , Tolboom Jules J. M. , Houwen Roderick H. J. , Norbruis Obbe F. , Derkx Bert H. F. , Taminiau Jan A. J. M.
Published: January 2024

Objective:

The purpose of this study was to describe the clinical experience with the anti–tumor necrosis factor chimeric monoclonal antibody, infliximab, in pediatric patients with Crohn disease in The Netherlands.

Design:

Descriptive.

Methods:

Clinical response and adverse effects of infliximab were recorded for pediatric patients with Crohn disease treated from October 1992 to January 2003.

Results:

Thirty patients (aged 7–18 years) with refractory Crohn disease (with or without severe fistulas) were treated with infliximab. Patients were treated with up to 30 infusions. Mean follow‐up was 25.3 months. A total of 212 infusions were administered. Thirteen patients had refractory Crohn disease without fistulas. Six patients showed good long‐term response to infliximab treatment (defined as clinical index ≤10 points). Sixteen patients had refractory Crohn disease with draining fistulas. Nine showed good long‐term response (closure or nonproductiveness of fistulas). One patient with metastatic Crohn disease in the skin had a good long‐term response. Six patients developed an allergic reaction during infusion. In one patient, the allergic reaction occurred after an infliximab‐free interval of 9 years. One patient died of sepsis.

Conclusions:

Infliximab was an effective therapy in 53% of patients with refractory pediatric Crohn disease, with or without fistulas. Approximately half of the patients become unresponsive to infliximab therapy. Randomized controlled studies are mandatory to assess long‐term efficacy and safety to define the optimal therapeutic strategy of infliximab therapy in children with Crohn disease.
Abnormal Oral Mucosal Light Reflectance in Infantile Hypertrophic Pyloric Stenosis
Authors: Parrini Stefano , Di Maggio Giovanni , Latini Giuseppe , Bianciardi Giorgio , Valdambrini Laura , De Felice Claudio
Published: January 2024

Objectives:

Infantile hypertrophic pyloric stenosis (IHPS) is the most common condition requiring surgical intervention during the first weeks of life. The etiology of IHPS is unknown, although both neuronal nitric oxide synthase upregulation and an extracellular matrix abnormality are suspected. Familial predisposition is an important feature. Phenotypical markers of IHPS, such as hypoplasia or agenesis of the inferior labial frenulum, have been described. The authors tested the hypothesis that IHPS is associated with abnormal reflectance of the oral mucosa.

Methods:

Twenty‐five children with surgically confirmed IHPS and 25 gender‐ and age‐matched control subjects participated in the study. Reflectance of the lower gingival and vestibular oral mucosa in the optical spectrum was measured using an imaging spectrophotometer.

Results:

Patients with IHPS had significantly higher light reflectance values in the violet, blue, blue‐green, green, yellow, and orange sections of the spectrum (all P values < 0.0001), with a maximum distance between group means at the 450‐nm wavelength (t‐value: 27.66, df = 48). A reflectance cutoff >5.26% at the 450‐nm wavelength identified patients with IHPS with 100% sensitivity and 100% specificity.

Conclusions:

This study reports a previously unrecognized mucosal reflectance abnormality of the oral mucosa in IHPS, thus offering a new, accurate, and noninvasive phenotypic marker for the condition.
A New Model for Studying Eosinophil Migration Across Cultured Intestinal Epithelial Monolayers
Authors: Michail Sonia , Abernathy Frank
Published: January 2024

Objective:

Eosinophils play an important role in some gastrointestinal inflammatory conditions. Stimulated eosinophils migrate across the vascular endothelial wall and into the intestinal epithelium where by‐products such as proteases may contribute to intestinal epithelial damage. Little is known about the epithelial migration of the eosinophils in the gut. The lack of data is attributable in part to the scarcity of human eosinophils for studies. HL‐60–differentiated eosinophils present a means to perform studies on eosinophil function and chemotaxis. HL‐60 clone 15 can be induced to differentiate into cells closely resembling human eosinophils. The authors describe a novel model for studying eosinophil migration across the intestinal epithelium.

Methods:

Fluorescent‐labeled HL‐60 eosinophils were incubated for 150 minutes on the basolateral surface of confluent and inverted T‐84 monolayers separated by fluoroblock insert membranes. Chemotactic gradients of n‐formyl methionyl leucyl phenylalanine (fMLP), eotaxin, and platelet aggregating factor (PAF) were used in variable concentrations. Changes in transepithelial electrical resistance (TEER) were compared with baseline values.

Results:

Differentiated HL‐60 eosinophils undergo migration in response to fMLP, PAF, and eotaxin. Migration is associated with a drop in TEER.

Conclusion:

In this model, HL‐60–differentiated eosinophils migrate in response to stimulants chemotactic for human eosinophils. The transepithelial migration of eosinophils is associated with epithelial barrier dysfunction, which may contribute to the development of disease.
Distinct targeting and uptake of platelet and red blood cell‐derived extracellular vesicles into immune cells
Authors: Ilvonen Petra , Pusa Reetta , Härkönen Kai , Laitinen Saara , Impola Ulla
Published: January 2024

Blood‐derived extracellular vesicles (EVs) hold great therapeutic potential. As blood contains mixed EV populations, it is challenging to study EVs originating from different cells separately. Blood cell concentrates manufactured in blood banks offer an excellent non‐invasive source of blood cell‐specific EV populations. To study blood cell‐specific EVs, we isolated EVs from platelet (TREVs) and red blood cell (EryEVs) concentrates and characterized them using nanoparticle tracking analysis, imaging flow cytometry, electron microscopy and western blot analysis and co‐cultured them with peripheral blood mononuclear cells (PBMCs). Our aim was to use imaging flow cytometry to investigate EV interaction with PBMCs as well as study their effects on T‐lymphocyte populations to better understand their possible biological functions. As a conclusion, TREVs interacted with PBMCs more than EryEVs. Distinctively, TREVs were uptaken into CD11c+ monocytes rapidly and into CD19+ B‐lymphocytes in 24 h. EryEVs were not uptaken into CD11c+ monocytes before the 24‐h time point, and they were only seen on the surface of lymphocytes. Neither TREVs nor EryEV were uptaken into CD3+ T‐lymphocytes and no effect on T‐cell populations was detected. We have previously seen similar differences in targeting PC‐3 cancer cells. Further studies are needed to address the functional properties of blood cell concentrate‐derived EVs. This study demonstrates that imaging flow cytometry can be used to study the distinctive differences in the interaction and uptake of EVs. Considering our current and previous results, EVs present a new valuable component for the future development of blood‐derived therapeutics.
Arc‐disjoint out‐branchings and in‐branchings in semicomplete digraphs
Authors: Bang‐Jensen J. , Wang Y.
Published: January 2024

An out‐branching (in‐branching ) in a digraph is a connected spanning subdigraph of in which every vertex except the vertex , called the root, has in‐degree (out‐degree) one. It is well known that there exists a polynomial algorithm for deciding whether a given digraph has arc‐disjoint out‐branchings with prescribed roots ( is part of the input). In sharp contrast to this, it is already NP‐complete to decide if a digraph has one out‐branching which is arc‐disjoint from some in‐branching. A digraph is semicomplete if it has no pair of nonadjacent vertices. A tournament is a semicomplete digraph without directed cycles of length 2. In this paper we give a complete classification of semicomplete digraphs that have an out‐branching which is arc‐disjoint from some in‐branching where are prescribed vertices of . Our characterization, which is surprisingly simple, generalizes a complicated characterization for tournaments from 1991 by the first author and our proof implies the existence of a polynomial algorithm for checking whether a given semicomplete digraph has such a pair of branchings for prescribed vertices and construct a solution if one exists. This confirms a conjecture of Bang‐Jensen for the case of semicomplete digraphs.
民間船舶を活用した災害医療(The possibility and usefulness of using civilian ships in times of disaster: Challenges of medical treatment on shipboard)
Authors: 航 野口 , 飛鳥 土谷 , 弘道 青木 , 誠司 守田 , 儀英 中川 , 吉彦 山田
Published: January 2024

【目的】第二次世界大戦以前，“病院船”は本邦においても運用されていたが，以降は姿を消した。近年災害時の“多目的船”として再び議論され，政府機関内の実証訓練を経て，2021年「災害時等における船舶を活用した医療提供体制の整備の推進に関する法律」が成立した。実際の民間船舶で実証訓練を行った結果から，災害時に提供可能な医療内容や活用する船舶における課題を抽出し検討した。【対象】学校法人東海大学が保有する海洋調査研修船『望星丸』内で「提供可能な医療」「患者搬送手段と方法」を検証する訓練を行った。軽症から中等症の16名の模擬患者に対し，DMATが乗船し診療，移動，療養管理を行った。【結果】船内常備およびDMATが持参する医療資機材で医療対応は可能であった。船室を活用し療養環境を確保できた。感染症対応は船外の通路を用いた動線分離が可能であった。車椅子，担架を用いて狭隘な通路や階段の移動は可能であった。訓練後アンケートより亜急性期の患者を収容し被災地外へ搬送する役割が期待された。【結語】既存の民間船舶であっても，船内設備を生かしつつ医療者が医療資機材を持ち込むことで，災害時に活用可能であることが示唆された。民間船舶の規模に応じた活用方法を平時から検討し，医療者・民間船舶の合同訓練を行うことで，民間船舶は災害時の有効なツールとなることが期待される。
ECMO脱血カニューレが上行腰静脈経由で下大静脈に留置されたが静脈造影下の抜去に成功した1例(A case of successful removal of an ECMO drainage cannula placed into the inferior vena cava via the ascending lumbar vein under venography)
Authors: 博之 本田 , 秀一郎 栗田 , 亨 松井 , さとみ 大橋 , 哲大 平田 , 陽祐 堀井 , 慶 西山
Published: January 2024

体外式膜型人工肺（extracorporeal membrane oxygenation: ECMO）施行時に超音波検査で脱血カニューレ先端が下大静脈–右房接合部に存在することを確認したにもかかわらず上行腰静脈迷入が判明した症例を経験した。症例は70歳代の男性。呼吸不全に対してveno–venous ECMOを導入した。脱血カニューレを挿入する際に抵抗があったが，心窩部超音波検査でガイドワイヤが下大静脈内にあることを確認していたため手技を続行した。その後，ECMOの血液流量が減少したため画像検索を行ったところ，脱血カニューレが上行腰静脈を経由して下大静脈に到達していることが判明した。抜去に際して出血の懸念があった。緊急手術に対応できるように準備し，脱血カニューレ内腔にバルーン付きガイドカテーテルを挿入して閉塞させ，静脈造影しつつ抜去した。出血時は静脈塞栓術を行う予定であったが出血は生じなかった。本症例のような迷入経路がありうるため，心窩部超音波検査のみではカニューレの上行腰静脈迷入を除外できない。下腹部超音波検査やX線撮影で確認することも考えられるが，時間に余裕があれば血管造影室で透視下にECMOを導入すべきである。迷入したカニューレを抜去する際にはバルーン付きガイドカテーテルを用いた静脈造影が選択肢の一つとなりうる。
Dorsoventral hippocampus distinctly modulates visceral sensitivity and anxiety behaviors in male IBS‐like rats
Authors: Lin Wei , Zhou Yifei , Liu Yuan , Liu Congxu , Lin Mengying , Tang Ying , Chen Aiqin , Wu Bin , Lin Chun
Published: January 2024

Accumulating evidences suggest dysfunctions in the hippocampus are associated with chronic pain. Nevertheless, the role of hippocampal circuitry in pain memories and emotional responses is not yet fully understood. In this study, we utilized a comprehensive approach that combined electromyography (EMG), photochemical genetic techniques, and anxiety‐related behavioral paradigms to investigate the involvement of dorsal hippocampus (DH) and ventral hippocampus (VH) in visceral sensitivity and anxiety behaviors in male rats. Our results demonstrated that IBS‐like rats exhibited comorbid visceral hypersensitivity and anxiety, along with the number of activated neurons in the VH was higher than that in the DH. Manipulation of glutamatergic neurons in the hippocampus was identified as a crucial mechanism underlying the mediation of both visceral sensitivity and anxiety behaviors. Specifically, optogenetic activation of the DH induced both visceral hypersensitivity and anxiety, while activation of the VH induced anxiety but did not affect visceral sensitivity. Conversely, chemogenetic inhibition of the DH reduced both visceral hypersensitivity and anxiety, whereas inhibition of the VH alleviated anxiety but did not alleviate visceral hypersensitivity in IBS‐like rats. Our study highlights the important role of early life stress in inducing visceral hypersensitivity and anxiety, and further elucidates the distinct functional contributions of the DH and VH to these behavioral changes. These findings provide a theoretical basis for the diagnosis and treatment of IBS, and suggest that targeting specific hippocampal neuron subtypes may represent a promising therapeutic approach.
Identification of cavotricuspid isthmus voltage patterns in typical atrial flutter ablation
Authors: Ribes Francisco , Ferrero‐de‐Loma‐Osorio Ángel , Sánchez‐Gómez Juan Miguel , Bondanza Lourdes , Martínez‐Brotons Ángel , Ruiz‐Granell Ricardo
Published: January 2024

Background

Electroanatomical mapping is an essential tool in the ablation of typical AFL.

Objectives

To identify the existence of voltage patterns in the CTI voltage maps and their relevance for typical AFL ablation.

Methods

A voltage map of the CTI was made prior to ablation, identifying the areas of maximum voltage and their location along the CTI, allowing classification into patterns according to their distribution. A stepwise ablation approach targeting the areas of maximum voltage was conducted. The ablation characteristics were compared based on the pattern obtained.

Results

Two voltage patterns were identified, with differences in ablation time to bidirectional CTI block. No complications occurred.

Conclusions

Voltage mapping identifies patterns in the CTI with implications for typical AFL ablation.
Raman study of the soft modification of graphene by femtosecond laser irradiation
Authors: Soto‐Puebla Diego , Alvarez‐Garcia Susana
Published: January 2024

Processing a graphene surface by irradiation with a fs‐pulsed laser at energies below the ablation threshold allows the production of non‐thermally modified regions with slightly different properties than pristine graphene. Oxidized nanoislands, optical forging, and nanopore networks are modifications of the graphene structure recently reported using a wide range of fs‐laser energies. In this work, we first determined the pulse energy threshold of a fs‐laser for the ablation of a commercial CVD graphene sample. Then we irradiated the sample in an extended range of pulse energies relative to the ablation threshold value. The irradiation process was simultaneously monitored by Raman spectroscopy, and the evolution of each Raman parameter (central position, bandwidth, and intensity) was analyzed. Special attention was given to the pulse energy that produced linear relationships between most Raman parameter pairs. These linear correlations evidence the interrelation between multiple Raman parameters and a soft processing method applicable to the controlled modification of the graphene lattice.