Evaluation of the efficiency of nanomicellar formulation of fat-soluble vitamins in patients with cystic fibrosis: the study protocol for a randomized controlled trial.

BACKGROUND: Cystic fibrosis is an inherited disease, which is caused by the CFTR protein defects due to mutations in the CFTR gene. Along with CFTR dysfunction, exocrine pancreatic insufficiency plays a key role in persistent fat malabsorption in CF patients; therefore, deficiency of fat-soluble vitamins (A, D, E, and K) is still a therapeutic challenge. Even with efficient pancreatic enzyme medication and CF-specific vitamins, many patients with CF have fat-soluble vitamins deficiency. The present study aims to evaluate the efficiency of nanomicelle formulation of fat-soluble vitamins in children with CF in order to achieve the appropriate serum levels of these vitamins. METHODS: This prospective, single-blind control trial will be conducted at the Akbar Children's Hospital in Mashhad, Iran. Patients with CF will be enrolled based on the eligibility criteria. The control group will receive the standard formulation of fat-soluble vitamins similar to the routine CF treatment, and for the intervention group, the nanomicelle formulation of fat-soluble vitamins will be administered for 3 months. The primary outcome of this study is the measurement of serum levels of fat-soluble vitamins. The secondary outcomes are clinical assessment by the Shwachman-Kulczycki score, anthropometrics, and quality of life. Outcomes will be assessed before and after 3 months. DISCUSSION: Due to persistent fat-soluble vitamin deficiency in CF disease, the nanomicelle formulation could be proposed as a new delivery method of fat-soluble vitamins in the treatment of cystic fibrosis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20220415054541N1. Registered on July 23, 2022.

Accuracy of hepatobiliary scintigraphy for differentiation of neonatal hepatitis from biliary atresia: systematic review and meta-analysis of the literature.

Hepatobiliary scintigraphy is an important diagnostic modality for work-up of neonatal cholestasis. Therefore, our objective was to evaluate the literature regarding the accuracy of hepatobiliary scintigraphy in differentiating biliary atresia from non-biliary atresia causes of cholestasis (collectively called neonatal hepatitis). Our search included Medline, SCOPUS and Google Scholar. Only studies using Tc-99 m-labeled immunodiacetic acid (IDA) derivatives were included. Overall, 81 studies were included in the meta-analysis. Pooled sensitivity and specificity were 98.7% (range 98.1-99.2%) and 70.4% (range 68.5-72.2%), respectively. Factors that increased specificity included the use of radiotracers with high hepatic extraction, administration of hepatic-inducing drugs (such as phenobarbital), use of a calculated dose/kg and administration of a booster dose in cases of non-excretion of the tracer in the bowel. SPECT imaging and duodenal fluid sampling also had high specificity; however, they need further validation because of the low number of studies. Semiquantitative imaging methods do not seem to have any incremental value. We conclude that hepatobiliary scintigraphy using IDA derivatives can be very useful for diagnostic work-up of neonatal cholestasis. To improve the specificity, several measures can be followed regarding type and dose of the radiotracer and imaging protocols. Non-imaging methods seem to be promising and warrant further validation.

Adjunctive nano-curcumin therapy improves inflammatory and clinical indices in children with cystic fibrosis: A randomized clinical trial.

Inflammation may develop due to internal dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) protein or external factors in patients with cystic fibrosis (CF). This prospective randomized clinical trial aimed to ascertain the effects of nano-curcumin as an anti-inflammatory agent and a CFTR modulator on clinical and inflammatory markers in children with CF. Children with CF were randomly assigned to receive daily curcumin or a placebo for 3 months. The primary outcome measure was to evaluate inflammatory indices, nasopharyngeal swab analysis, and clinical assessments via spirometry, anthropometric measurements, and quality of life (QOL) analysis. Sixty children were included. Intra-group changes comparison showed that curcumin decreased the level of high-sensitivity C-reactive protein (hs-CRP) (median: -0.31 mg/L, IQR: -1.53 to 0.81; p = .01) and fecal calprotectin level (-29 µg/g, -57.5 to 11.5; p = .03), also increased the level of interleukin (IL)-10 (6.1 pg/mL, 4.5-9; p = .01). Moreover, curcumin improved the overall QOL and the subscales of the questionnaire. Inter-group changes comparison depicted the number of Pseudomonas colonies reduced by about 52% in the curcumin group and gained weight by about 16% (p > .05). Nano-curcumin seems to be considered as an effective nutritional supplement on hs-CRP, IL-10, fecal calprotectin levels, and improving QOL in patients with CF.

COVID-19 infection in an infant with cystic fibrosis: A case report and possible therapeutic effect of hypertonic saline.

Pulmonary infections represent the major causes of morbidity and mortality in cystic fibrosis (CF). Here, we report a 3-month-old infant with pancreatic insufficient CF was hospitalized with positive RT-PCR test for COVID-19. He was treated successfully. Hypertonic saline can be hypothesized as a treatment regimen against COVID-19 infection after further investigations.

Impact of Chronic Functional Constipation on Lower Urinary Tract System: A Cases - Control Study.

INTRODUCTION: Association of constipation with incomplete bladder emptying, functional bladder outlet un-coordination, urinary tract infection (UTI), and upper urinary tract dilatation has been reported. We designed a study to determine the impact of chronic functional constipation on kidney and bladder ultrasound parameters, the results of the uroflowmetry test, and its association with UTI. METHODS: The study group consisted of 24 cases and 48 controls, who were children between 5 to 18 years-old, from June 2017 to June 2018. The case group included children with chronic functional constipation. The healthy children with urinary continence and regular bowel habits without any history of UTI were considered as the control group. The variables were bladder volume, postvoiding urinary residual volume, full and empty bladder wall thicknesses, uroflowmetry parameters and, UTI prevalence. RESULTS: There were no significant differences in the prevalence of UTI, upper urinary tract dilatation on kidney ultrasound, uroflowmetry and, bladder ultrasound parameters between the case and control groups (P > .05 for all). We found abnormal uroflowmetry curves in 58.3% and 35.4% of the case and control groups, respectively (P > .05) and a higher rate of staccato curves in constipated compared to healthy children. CONCLUSION: the prevalence of UTI and upper urinary tract dilatation on kidney ultrasonography are not significantly different between constipated and healthy children. Moreover, it seems that chronic constipation has no significant impact on the storage and emptying functions of the bladder. The higher frequency of staccato curves in constipated compared to healthy children can indicate that fecal mass causes detrusor sphincter dyssynergia.  DOI: 10.52547/ijkd.6568.

Fecal Calprotectin and Phenotype Severity in Patients with Cystic Fibrosis: A Systematic Review and Meta-Analysis.

Inflammation plays an important role in the outcome of patients with cystic fibrosis (CF). It may develop due to cystic fibrosis transmembrane conductance regulator protein dysfunction, pancreatic insufficiency, or prolonged pulmonary infection. Fecal calprotectin (FC) has been used as a noninvasive method to detect inflammation. Therefore, the aim of the current meta-analysis was to investigate the relationship between FC and phenotype severity in patients with CF. In this study, searches were conducted in PubMed, Science Direct, Scopus, and Embase databases up to August 2021 using terms such as "cystic fibrosis," "intestine," "calprotectin," and "inflammation." Only articles published in English and human studies were selected. The primary outcome was the level of FC in patients with CF. The secondary outcome was the relationship between FC and clinical severity. Statistical analysis was performed using Comprehensive Meta-Analysis software. Of the initial 303 references, only six articles met the inclusion criteria. The mean (95% confidence interval [CI]) level of FC was 256.5 mg/dL (114.1-398.9). FC levels were significantly associated with pancreatic insufficiency (mean, 243.02; 95% CI, 74.3 to 411.6; p=0.005; I2=0), pulmonary function (r=-0.39; 95% CI, -0.58 to -0.15; p=0.002; I2=60%), body mass index (r=-0.514; 95% CI, 0.26 to 0.69; p<0.001; I2=0%), and Pseudomonas colonization (mean, 174.77; 95% CI, 12.5 to 337.02; p=0.035; I2=71%). While FC is a reliable noninvasive marker for detecting gastrointestinal inflammation, it is also correlated with the severity of the disease in patients with CF.

Risk factors associated with life-threatening infections in children with febrile neutropenia: a data mining approach.

PURPOSE: To determine risk factors (RFs) and their relationship with life-threatening infection (LTI) in children with febrile neutropenia (FN). METHOD: In this cross-sectional study, from December 2008 to November 2009, all children with FN admitted to Dr Sheikh Pediatric Hospital were enrolled. For each patient, demographic, clinical, and laboratory data were recorded and they were followed up for occurrence of LTI. RESULTS: One hundred and twenty episodes of FN in 68 patients were analyzed. The most common underlying disease was acute lymphoblastic leukemia (53.3%), 9 (7.5%) died from an infection and 35 patients (29.1%) had a LTI. Five variables were identified as RFs for LTI, that is, body temperature ≥39°C (P=0.000), presence of mucositis (P=0.000), abnormal chest x-ray (P=0.001), platelet count <20,000/mm (P=0.000), and absolute neutrophil count <100/mm (P=0.001). Risk of LTI was increasing according to number of RFs presented at the beginning of admission (from 2.8% in patients without RF to 100% in patients with 5 RF). Data mining analysis showed relationship between RFs with platelet count as the most important variable in the high-risk group for LTI. CONCLUSIONS: Evaluation of important RFs and judging the severity of patients' condition by studying the importance and relationship between RF at the time of admission can be a useful method for screening LTI in children with FN.

The effects of nano-curcumin as a nutritional strategy on clinical and inflammatory factors in children with cystic fibrosis: the study protocol for a randomized controlled trial.

BACKGROUND: Cystic fibrosis (CF) is a genetic disorder, which is caused by the CFTR protein defects. Along with CFTR dysfunction, inflammation plays a key role in the disease outcomes. Inflammation may develop due to the internal dysfunction of the CFTR protein or external factors. Curcumin affects the CFTR protein function primarily as a corrector and potentiator and secondary as an anti-inflammatory and antimicrobial agent. The present study aims to assess the impact of nano-curcumin on clinical and inflammatory markers in children with CF. METHODS: This prospective, double blind control trial will be conducted at the Akbar Children's Hospital in Mashhad, Iran. Children with CF will be enrolled based on the eligibility criteria. Placebo and curcumin with the maximum dose of 80 mg considering the body surface of the patients will be administrated for 3 months. The primary outcome is to evaluate inflammation based on serum interleukin-6, interleukin-10, and hs-CRP, stool calprotectin, and neutrophil count of nasopharyngeal swab. The secondary outcome involved clinical assessment via spirometry, anthropometrics, and quality of life. They will be assessed before and after 3 months. DISCUSSION: Due to the multifarious effects of curcumin on CF disease, it could be proposed as a nutritional strategy in the treatment of cystic fibrosis. TRIAL REGISTRATION: Iranian Registry of Clinical Trials IRCT20200705048018N1 . Registered on July 10, 2020.

How to Boost our Immune System Against Coronavirus Infection?

New emerging viruses like coronavirus 2019 (COVID-19) infections are always frightening. We know little about their transmission, behaviors, clinical manifestations, and outcomes. There is no vaccine or therapeutic strategies to deal with these infections yet. In this situation, preventive measures may be promising. Hand hygiene is a very important issue in preventing viral infection; however, there are other entities that can enhance the immune response and help in infection prevention. Herein we review some measures for boosting the immune system.

99mTc sestamibi imaging - can it be a useful substitute for hepatobiliary scintigraphy in infantile jaundice?

AIM: Hepatobiliary scintigraphy is an integral part in the diagnostic work-up of the neonatal cholestasis syndrome. However, less than optimal specificity is its major disadvantage. Differentiation between biliary atresia and neonatal hepatitis is nearly impossible in some cases with poor hepatocellular function. 99mTc sestamibi (MIBI) is a cationic lipophilic agent which is a substrate of P-glycoprotein. This glycoprotein is normally expressed in biliary canalicular surfaces of hepatocytes. This property provides a hepatic excretory mechanism which is different from bilirubin excretion. In this study we evaluated the value of 99mTc MIBI in differential diagnosis of neonatal cholestasis. PATIENTS, METHODS: 20 infants with a mean age of 2.41 months (range, 0.1-5 months) were included in the study. Ten infants turned out to have extrahepatic biliary atresia and the other ten had neonatal hepatitis. Hepatobiliary (with 99mTc BrIDA) and 99mTc MIBI scintigraphy were performed for all the patients. RESULTS: 99mTc MIBI scintigraphy has shown bowel activity in all patients, including the patients with biliary atresia. Hepatobiliary scintigraphy revealed bowel activity only in five patients with neonatal hepatitis. CONCLUSION: Bowel visualization with 99mTc MIBI may be seen in patients with biliary atresia and 99mTc MIBI has limited value in differential diagnosis of neonatal cholestasis.

Intrapulmonary arteriovenous shunt in children with chronic liver disease: clinical features, laboratory data and outcome.

OBJECTIVE: To determine the frequency of hepatopulmonary syndrome in children with chronic liver disease, and its clinical and biochemical associations. METHOD: This study included 53 children with chronic liver disease, who underwent contrast echocardiography with agitated saline and measurement of arterial blood gases. RESULTS: Of the 53 patients studied, 18 had intrapulmonary shunting of blood. This shunting was associated with presence of palpable spleen, cyanosis and dyspnea, but not with abnormalities in the biochemical tests of liver function. At 1-year follow-up, there were 5 deaths among 18 patients with intrapulmonary shunt. In a logistic regression model, PaO 2 < 70 mmHg was found to be a predictor of death (p< 0.05). CONCLUSION: Intrapulmonary shunting is a common and important complication in children with chronic liver disease.

Etiology of gastrointestinal bleeding in children referred to pediatric wards of Mashhad hospitals, Iran.

BACKGROUND: Gastrointestinal (GI) bleeding, which has several clinical manifestation and origins, is known as one of the most life-threatening events in children. Several etiologies have been suggested for GI bleeding. OBJECTIVE: To determine the most important causes of GI bleeding in children referred to Ghaem Hospital and Dr. Sheikh Hospital, Mashhad, Iran. METHODS: In this cross-sectional study, after obtaining written informed consent of their parents, 113 patients aging from newborn infants to 18-year-old children with GI bleeding admitted to Ghaem Hospital and Dr. Sheikh hospital were enrolled in this study from June 2012 to June 2014. After performing routine diagnostic and therapeutic procedures, a checklist containing all necessary information including demographic data, clinical history of patients, endoscopy and pathology findings, clinical and preclinical information were collected. The data were then analyzed using Statistical Package for the Social Sciences (SPSS) version 16. RESULTS: Of a total 113 study children, 61 (54%) were male and 52 (46%) were female. The results of this study showed that the most important causes of bleeding in upper GI among all admitted patients were prolapse gastropathy (18.6%), esophagitis (15.9%) and esophageal varices, gastritis, and coagulopathy (7.1% for each). The main causes of lower GI bleeding were polyp (32.5%), chronic nonspecific colitis (20.7%), and proctitis (18.2%). CONCLUSION: Findings of this study indicated that prolapse gastropathy and esophagitis are more prevalent causes of upper GI bleeding. Furthermore, esophageal varices were more common in children older than 13 years. Polyp, chronic nonspecific colitis and proctitis are the most prevalent causes of lower GI bleeding.

D28G mutation in congenital glucose-galactose malabsorption.

BACKGROUND: Congenital glucose-galactose malabsorption is a rare autosomal recessive disorder of the intestinal transport of glucose and galactose, leading to watery diarrhea, dehydration, failure to thrive, and early death. METHODS: In this study, we analyzed D28G mutation in 16 family members of a patient with typical presentation of congenital glucose-galactose malabsorption with polymerase chain reaction-Restriction Fragment Length Polymorphism method. RESULTS: Nine members of this family were heterozygous for D28G mutation. CONCLUSION: To the best of our knowledge this is the first report of D28G mutation in Iran. Moreover, this simple typical PCR-Restriction Fragment Length Polymorphism method, allows immediate identification of D28G mutation.

Effect of oral garlic on arterial oxygen pressure in children with hepatopulmonary syndrome.

AIM: To study the effect of oral garlic on arterial oxygen pressure in children with hepatopulmonary syndrome. METHODS: Garlic powder in a capsule form was given to 15 children with hepatopulmonary syndrome (confirmed by contrast echocardiography) at the dosage of 1 g/1.73 m(2) per day. Patients were evaluated clinically and by arterial blood gas every four weeks. RESULTS: The garlic capsule was administered to 15 patients with hepatopulmonary syndrome. There were 10 boys and 5 girls with a mean age of 9.4+/-3.9 years. The underlying problems were biliary tract atresia (4 patients), autoimmune hepatitis (4 patients), cryptogenic cirrhosis (4 patients) and presinusoidal portal hypertension (3 patients). Eight patients(53.3%) showed an increase of 10 mmHg in their mean arterial oxygen pressure. The baseline PaO(2) was 65.6+/-12.1 mmHg in the responder group and 47.1+/-11.2 mmHg in non-responder group. At the end of treatment the mean PaO(2) in responders and non-responders was 92.2+/-7.75 mmHg and 47.5+/-11.87 mmHg, respectively (P<0.01). CONCLUSION: Garlic may increase oxygenation and improve dyspnea in children with hepatopulmonary syndrome.

Sensitivity Comparison of the Skin Prick Test and Serum and Fecal Radio Allergosorbent Test (RAST) in Diagnosis of Food Allergy in Children.

BACKGROUND: Diagnosis of food allergy is difficult in children. Food allergies are diagnosed using several methods that include medical histories, clinical examinations, skin prick and serum-specific immunoglobulin E (IgE) tests, radio-allergosorbent test (RAST), food challenge, and supervised elimination diets. In this study we evaluated allergies to cow's milk, egg, peanut, and fish in children with suspected food allergies with skin prick tests and serum and feces RAST. METHODS: Forty-one children with clinical symptoms of food allergies were enrolled in the study. Skin prick tests and serum and fecal RAST were performed and compared with challenge tests. RESULTS: The most common sites of food allergy symptoms were gastrointestinal (82.9%) and skin (48.8%). 100% of the patients responded to the challenge tests with cow's milk, egg, peanut, and fish. 65% of the patients tested positive with the skin prick test, 12.1% tested positive with serum RAST, and 29.2% tested positive with fecal RAST. CONCLUSION: The skin prick test was more sensitive than serum or fecal RAST, and fecal RAST was more than twice as sensitive as serum RAST.

A Case with Complete Pancreatic Aplasia Suggestive of Johanson-Blizzard Syndrome.

Johanson-Blizzard Syndrome (JBS) is a very rare autosomal recessive multisystem disorder. We report the case of a two-month-old male with pancreatic insufficiency and severe phenotypic features. His diagnosis of JBS was established using clinical symptoms and abdominal computed tomography scan that showed pancreas aplasia. According to the best of our knowledge, no case with this syndrome has presented with complete pancreatic aplasia in the literature.

Isolated Splenic Vein Thrombosis: 8-Year-Old Boy with Massive Upper Gastrointestinal Bleeding and Hypersplenism.

We present an 8-year-old boy who was referred to our center with the complaint of upper gastrointestinal bleeding and was diagnosed with hypersplenism and progressive esophageal varices. Performing a computerized tomography (CT) scan, we discovered a suspicious finding in the venography phase in favor of thrombosis in the splenic vein. Once complementary examinations were done and due to recurrent bleeding and band ligation failure, the patient underwent splenectomy. And during the one-year follow-up obvious improvement of the esophageal varices was observed in endoscopy.

99mTc-Pertechnetate imaging for detection of ectopic gastric mucosa: a systematic review and meta-analysis of the pertinent literature..

BACKGROUND AND AIMS: 99mTc-pertechnetate scintigraphy has long been used for detection of ectopic gastric mucosa (EGM) in the medical practice and evaluation of children with lower gastrointestinal bleeding. In the current study, we reviewed the available medical literature in this regard. METHODS: Medline and SCOPUS were searched for relevant studies. Studies with sample size of at least 5 patients which provided enough numerical data to calculate the sensitivity and/or specificity of 99mTc-pertechnetate for detection of EGM were includ ed in the systematic review. RESULTS: Overall 40 studies were included in our systematic review. Overall diagnostic indices of the 99mTc-pertechnetate scintigraphy for EGM diagnosis were: sensitivity 92.1% [95% CI: 90.2-93.8], specificity 95.4% [943-963], positive likelihood ratio 16.5 [9.9-27.], negative likelihood ratio 0.15 [0.1-0.2], diagnostic odds ratio 120.7 [73-199]. The pooled sensitivity was higher for studies using H2 blockers as a premedication (92.4% vs. 86.4%), studies using delayed imaging (943% vs. 88.4%), children (92.3% vs. 81.8%), and patients with gastrointestinal bleeding (953% vs. 75.3%). CONCLUSIONS: 99mTc-pertechnetate imaging is a highly accurate diagnostic modality for detection of EGM. This imaging is more accurate in children and patients presenting with gastrointestinal bleeding. Premedication with H2 blockers and delayed imaging can increase the diagnostic accuracy and should be routinely included in the imaging protocol.

Synbiotics in Children with Cow's Milk Allergy: A Randomized Controlled Trial.

OBJECTIVE: Cow`s milk protein allergy usually occurs in infants within the first months of life. It can affect several organs, but gastrointestinal symptoms are the most clinical symptoms observed. The most effective treatment is restricting the cow `s milk protein in mother and infant`s diet. Lactobacillus GG supplementation in infant could be effective through modulation of the immune system and the gut microflora. METHODS: Thirty two breastfed infants with cow`s milk protein allergy were enrolled in a double-blinded randomized controlled trial in which they received Synbiotic (n=16) or placebo (n=16) once a day for one month, simultaneously with cow`s milk protein restriction in mother and infant`s diet. Clinical gastrointestinal symptoms (vomiting, colic, rectal bleeding and diarrhea), head circumference, body length and weight were recorded at the beginning, the end of the first and third month of study. Findings : Percentage of increment in head circumference and weight were statistically more in synbiotic group compared with placebo group at the end of the first and third month of study. There was no significant difference in resolution of clinical gastrointestinal symptoms (vomiting, colic, rectal bleeding or diarrhea) and percentage of increment in body length. CONCLUSION: Synbiotic supplementation in infants may improve increment of head circumference and weight gain, but has no effect on resolution of clinical symptoms.

Dermatoglyphic patterns in cystic fibrosis children.

OBJECTIVE: It is believed that fingerprints and palm patterns may represent genetically determined congenital abnormalities in Cystic Fibrosis (CF). The main idea of this paper was to determine differences of fingerprints and palm patterns in CF and normal children. METHODS: Forty-six CF children (27 males, 19 females) and 341 (113 males, 228 females) healthy individuals were recruited for this study. Fingerprint patterns, Total ridge count (TRC) of each finger, a-b ridge count, and atd angles of all participants were recorded. Asymmetry of the right and left hand for each value was determined and dissimilarity in fingerprint patterns between homologous fingers was compared using Chi-square analysis, Mann-Whitney U test and Fisher's exact test. FINDINGS: There were significant differences in the mean TRC of the right digit IV (P=0.009), left digit III (P=0.02), left digit IV (P=0.03), and left digit V (P=0.03). Furthermore, we found significant differences in right atd angel (P=0.001), left atd angel (P=0.002), right a-b ridge (P=0.007) and left a-b ridge (P=0.001). In contrast, we found no significant differences in atd angle asymmetry, a-b ridge count asymmetry and pattern dissimilarity score between both groups (P>0.05). CONCLUSION: Dermatoglyphic characteristics could be used as a supplementary diagnostic method in CF children.