Genomic testing identifies monogenic causes in patients with very early-onset inflammatory bowel disease: a multicenter survey in an Iranian cohort.

Patients with very early-onset inflammatory bowel disease (VEO-IBD) may present because of underlying monogenic inborn errors of immunity (IEI). Strong differences have been observed in the causes of monogenic IBD among ethnic populations. This multicenter study was carried out on 16 Iranian patients with VEO-IBD. We reviewed clinical and basic immunologic evaluation including flow cytometry and immunoglobulin levels. All patients underwent clinical whole exome sequencing (WES). Sixteen patients (8 females and 8 males) with a median age of 43.5 months were enrolled. The median age at the onset of symptoms was 4 months. Most patients (12, 75%) had consanguineous parents. Chronic non-bloody diarrhea (13, 81.3%) and perianal diseases including perianal abscess (6, 37.5%), anal fissure (6, 37.5%), or anal fistula (2, 12.5%) were the most common manifestations. WES identified a spectrum of genetic variants in 13 patients (81.3%): IL10RB (6, 37.5%), MVK (3, 18.8%), and CASP8, SLC35C1, G6PC3, and IKBKB in 1 patient, respectively. In 3 patients (18.7%), no variant was identified. Flow cytometry identified a spectrum of abnormalities that helped to assess the evidence of genetic diagnosis. At the end of the survey, 3 (18.8%) patients were deceased. This high rate of monogenic defects with a broad spectrum of genes reiterates the importance of investigating IEI in patients with infantile-onset IBD.

Hyperuricosuria and hypercalciuria, probable etiologies of functional abdominal pain: A case-control study.

Background: Functional abdominal pain (FAP) is a common complaint causing several referrals to pediatricians. On the other hand, the most common presentation of hyperuricosuria and also hypercalciuria is chronic/recurrent abdominal pain. Therefore, a hypothesis has been raised; abdominal pain due to hyperuricosuria and/or hypercalciuria may be misdiagnosed as FAP. The current study has aimed to respond to this theory. Materials and Methods: This is a case-control study conducted on children diagnosed with FAP based on Rome IV criteria and age-matched normal controls. Blood and random urine samples were taken from healthy children and those with FAP. Random urine samples were examined for calcium, uric acid, oxalate, and creatinine concentrations. Random urine calcium to urine creatinine above 0.2 mg/mg was considered hypercalciuria and random urine uric acid above 0.56 mg/dl, GFR as hyperuricosuria. The data were analyzed using logistic models. Results: Hypercalciuric children had a significantly lower chance of FAP (odds ratio [OR] =0.425, 95% confidence interval [CI] =0.204-0.886). Although an inverse association was seen between hyperuricosuria and FAP (OR = 0.693, 95% CI = 0.395-1.214), it was not statistically significant. In stratified analyses by gender for both hyperuricosuria and hypercalciuria, a marginal inverse significant association was seen in male gender (P < 0.1). Conclusion: Our study showed that hypercalciuria is significantly in inverse association with FAP but not hyperuricosuria. Therefore, these disorders, particularly hyperuricosuria may not be considered as the possible causes of FAP. Further studies with larger sample size for providing more reliable evidence are recommended.

The correlation between viral shedding duration and blood biomarkers in COVID-19-infected patients.

Background: Since December 2019, the world is struggling with an outbreak of coronavirus disease-2019 (COVID-19) infection mostly represented as an acute respiratory distress syndrome and has turned into the most critical health issue worldwide. Limited information is available about the association between dynamic changes in the naso/oropharyngeal viral shedding in infected patients and biomarkers, aiming to be assessed in the current study. Materials and Methods: This quasi-cohort study was conducted on 31 patients with moderate severity of COVID-19 manifestations, whose real-time polymerase chain reaction (RT-PCR) test was positive for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) RNA at baseline. RT-PCR was rechecked for patients every 3-4 days until achieving two negative ones. In parallel, biomarkers, including lymphocyte count, lactate dehydrogenase (LDH), and C-reactive protein (CRP), were assessed every other day, as well. Viral shedding also was assessed. Results: Spearman's correlation test revealed a significant direct correlation between the viral shedding from the symptom onset and the time, in which CRP (P = 0.0015, r = 0.54) and LDH (P = 0.001, r = 0.6207) return to normal levels after symptom onset, but not for lymphocyte count (P = 0.068, r = 0.34). Conclusion: Based on the current study's findings, the duration of SARS-CoV-2 RNA shedding was directly correlated with the required time for LDH and CRP return to normal levels. Therefore, these factors can be considered the determinants for patients' discharge, isolation, and return to social activities; however, further investigations are required to generalize the outcomes.

Food allergy among Iranian children with inflammatory bowel disease: A preliminary report.

BACKGROUND: Evidence has shown a link between allergic disease and inflammatory bowel diseases (IBDs). We investigated food allergy in Iranian pediatric IBD patients. MATERIALS AND METHODS: A cross-sectional study was conducted on a consecutive sample of children with newly diagnosed IBD referring to Mofid Children's University Hospital in Tehran (Iran) between November 2013 and March 2015. Data on age, gender, history of cow's milk allergy (CMA), IBD type, routine laboratory tests, and colonoscopic and histopathological findings were gathered. Food allergy was assessed with the skin prick test (SPT). RESULTS: A total of 28 patients including 19 ulcerative colitis (UC), 7 Cronh's disease (CD), and two with unclassified colitis with a mean age of 8.3 ± 4.4 years. (57.1% females, 42.9% were studied. History of CMA was present in eight patients (28.6%). Seventeen patients (60.7%) had at least one food allergy (68.4% of UC vs. 42.9% of CD, P = 0.230). Ten patients (35.7%) had multiple food allergies (36.8% of UC vs. 42.9% of CD, P > 0.999). Common allergic foods were cow's milk (28.6%), beef, seafood, albumen, wheat, and walnuts (each 10.7%), and peanuts and chestnuts (each 7.1%). The SPT showed CMA in 68.4% (8/17) of UC but none of the CD patients (P = 0.077). CONCLUSION: Food allergy is frequent in Iranian pediatric IBD patients with CMA being the most common observed allergy. The CMA seems to be more frequent in UC than in CD patients.

Does Gabapentin Have A Role in the Improvement of Feeding Resistance in Infants?

Background: Eating disorders in some infants can be due to the inability to reach a level of relaxation necessary to start the feeding process. Gabapentin (GB) has been proposed as a stabilizer of nerve function in improving this disorder. This study aimed to investigate the effect of GB on improving feeding resistance in infants aged 3-6 months. Materials and Methods: This randomized, controlled, double-blind clinical trial was done on 64 infants aged 3-6 months with feeding resistance who were referred to the pediatric clinics and assigned to two groups of 32. The case group was given a dose of 5 mg/kg of GB in the first week, and if not too much sedation, it was increased to 10 mg/kg in the second week every 8 hours, whereas the control group received a placebo. The number of effective breastfeeding and the volume of formula in cc before and after 2 weeks of drug usage were recorded in both groups. Results: The number of breastfeeding sessions significantly had a higher increase in the GB group compared with placebo (median [IQR]: 1 [0,1] vs. 0 [0,1], P = 0.005) as well as an increase in consumed formula volume (mean ± SD: 42.81 ± 24.49 vs. 18.67 ± 14.57, P = 0.003). Conclusion: Considering the significant increase in formula consumption and the number of breastfeeding sessions in the GB group, it is possible to use this drug as a nerve-stabilizer and pain reducer to treat this disorder.

Treatment methods for oesophageal strictures in paediatric patients with epidermolysis bullosa: a systematic review.

BACKGROUND: Epidermolysis bullosa (EB) is a collection of rare, inherited disorders that require treatment in specialised centres by multidisciplinary teams knowledgeable about the unique features and challenges of EB manifestations and complications.A major gastrointestinal complication in patients with EB is oesophageal strictures. Effective management of oesophageal strictures can significantly improve patients' quality of life. This study systematically reviews the current literature on treatment options for oesophageal strictures in paediatric patients with EB. METHODS: In September 2023, we conducted a systematic search for articles on the treatment of oesophageal stricture in patients with EB. We searched PubMed, Scopus, Embase and Ovid database without language or publication date restrictions. We screened 1042 articles, 15 of them were included in the current review. We extracted the following data from these studies: patient demographics, stricture characteristics, procedural details, clinical outcomes, complications and recurrences. RESULTS: Overall, in the reviewed papers, strictures were located mostly in cervical oesophagus followed by thoracic lesions. Moreover, in most of the cases only a single stricture was reported, but multiple strictures were not uncommon. Stricture treatment approaches included medical management, bougienage, as well as fluoroscopic and endoscopic balloon dilation or a combination of these methods. In most studies, fluoroscopic dilation was used as the primary treatment method in 756 procedures. They commonly used general anaesthesia for the procedure, only one study used sedation. Hospital stays were usually brief, with an average duration of 1 day, and in one study patients were discharged after just 4 hours. Most patients experienced symptom relief, could resume oral intake and gained weight soon after the procedure. However, recurrence rates had large variations from 12% to 83%. Studies reported median recurrence intervals ranging from 7 to 18 months. This review showed that complications such as perforation, fever and odynophagia were relatively uncommon, and were controlled by conservative treatment. CONCLUSIONS: Both fluoroscopic and endoscopic balloon dilation are widely used methods for the management of oesophageal strictures in patients with EB. Each technique presents its own set of advantages and potential complications. Although the current evidence is notably limited, practical clinical decision-making may favour the fluoroscopic technique over endoscopic balloon dilation due to a comparatively reduced risk of procedural trauma. To ascertain the most effective approach, high-quality randomised controlled trials are imperative to delineate the superiority of one technique over the other.

Comparison of Blood Lead Levels in Children and Adolescents with and without Functional Abdominal Pain.

Background: Functional abdominal pain is a health concern with chronic abdominal discomfort without clear etiology. Several etiologic factors are raised in this regard, one related to environmental factors. This study aimed to compare blood lead levels between children and adolescents with and without functional abdominal pain. Materials and Methods: This case-control study was performed in 2019-2020 in Isfahan, Iran. The sample size was calculated as 70 cases and an equal number of controls. Cases were children and adolescents with functional gastrointestinal disorder (FGID), and controls were grouped age- and sex-matched. Controls were randomly selected from those referred for routine health screening. Both groups obtained blood lead, iron, and calcium levels. All participants completed the FFQ Food Consumption and Environmental Pollutants Questionnaire. Results: Participants were 139 children (68 cases and 71 controls). The mean (SD) age was 9.40 (3.91) years in the FGID group and 8.79 (3.46) years in the controls (P = 0.330). The mean (SD) blood lead level was not significantly different between the FGID group and the controls (3.98 ± 2.56 vs 3.81 ± 1.96 µg/dl, respectively, P = 0.670). We found that 55.3% of children with high lead levels had FGID, while 44.4% of children with lower lead levels had FGID, but the difference was not statistically significant (P = 0.33). Conclusion: We found that the lead level was higher in patients with FGID than in the controls; however, this difference was not significantly different. This might be because of elevated lead levels in both groups. Future ecological studies with a large sample size are necessary in this regard.

Helicobacter pylori infection in pediatrics with gastrointestinal complaints.

BACKGROUND: Helicobacter pylori is one of the most important pathogenic bacteria in gastric mucosa both in adults and pediatrics. Here we aimed to investigate the prevalence of Helicobacter pylori in pediatrics with gastrointestinal complaints by the endoscopic method and using pathology reports. METHODS: This is a cross-sectional study that was performed in 2019-2020 in Imam Hossein hospital affiliated to Isfahan University of Medical Sciences on medical documents of pediatrics that underwent gastric or duodenal biopsy via endoscopy. We collected data regarding patients' age, gender, place of residence, type of gastrointestinal complaints, and prevalence of Helicobacter pylori infection from the medical reports. We also investigated the possible correlation between the presence of Helicobacter pylori and the type of complaints among patients. RESULTS: A total number of 400 pediatrics entered the study. Abdominal pain was the most common complaint (42%). Helicobacter pylori infection was found in 31 cases (7.8%). The prevalence of Helicobacter pylori infection in boys (10.7%) was significantly higher than in girls (4.6%) (P = 0.02) and was significantly related to the age group of children (P<0.001) in the way that Helicobacter pylori infection was more common in higher ages. There was no significant relationship between the prevalence of Helicobacter pylori infection and the type of complaint (P = 0.29). CONCLUSION: We showed that the prevalence of Helicobacter pylori infection is low among pediatrics with gastrointestinal complaints and this issue could cast doubt on the high prevalence rates and importance of this infection in children.

The Effectiveness of Synbiotic on the Improvement of Clinical Symptoms in Children with Eosinophilic Esophagitis.

Background: Eosinophilic esophagitis (EoE) is an allergic inflammatory disorder of the esophagus. Today, probiotics are included as adjuvant therapy in the treatment of allergic diseases. The aim of this study was to assess the effect of synbiotic on clinical symptom improvement in EoE patients. Methods: This study is designed by a double-blind, placebo-controlled clinical trial with two parallel groups, which was performed on 30 children with eosinophilic esophagitis. All participants were children aged 6 months to 15 years. Both groups received the same treatment (elimination diet, topical steroid, and proton pump inhibitor). A synbiotic (KidiLact) was added to the medication regimen of 15 patients (case), while the next 15 patients received a placebo (control). Severity and frequency of symptoms were assessed with a checklist derived from a validated scoring tool in both groups before and after 8 weeks of treatment. Results: There was a significant reduction in the severity score of chest pain and poor appetite (P value < 0.05) in the case group taking probiotics, while nausea and poor appetite were the only symptoms with a significant reduction in the frequency score after intervention in this group. Conclusion: Probiotics can be used as adjuvant treatment for patients with EoE. Improvement in the severity of chest pain and poor appetite and reduction in the frequency of nausea and poor appetite in these patients can be seen.

On-admission versus in-hospital thromboembolism due to COVID-19 infection. What is the particular characteristic of those with early thrombotic events?

INTRODUCTION: Increasing evidence has declared a hypercoagulable state in the coronavirus 2019 infection (COVID-19), while the etiology has remained a question. For the first time, the current study has aimed to compare the contributors of thromboembolism among those whose primary manifestations of COVID-19 were thrombosis vs the patients with a thrombotic event during the period of hospitalization. MATERIAL AND METHODS: This case-control study has been conducted on 267 COVID-19 patients, including 59, 48, and 160 ones with an on-admission, in-hospital, and without a thrombotic event, respectively. The events were defined as deep vein thrombosis (DVT), ischemic cerebrovascular accidents (CVA), pulmonary thromboembolism (PTE), or acute myocardial infarction (AMI). The demographic, physical examination, clinical and laboratory assessments of the groups were compared. RESULTS: The DVT (OR: 5.18; 95% CI: 1.01-26.7), AMI (OR: 11.1; 95% CI: 2.36-52.3), and arterial thrombosis (OR: 5.93; 95% CI: 0.63-55.8) were significantly associated with an on-admission thrombosis compared to those who presented in-hospital events. Lower levels of oxygen saturation were the only significant predictor index inversely associated with on-admission thrombosis compared to those with an event during the hospital admission period. CONCLUSION: PTE development was the most common in-hospital thrombotic event, whereas other thromboembolism types were remarkably more often among cases with on-admission events. Oxygen saturation was the only predictor of premature thrombosis that was inversely associated with outpatient events.

The demographic, clinical, and medical manifestations of pulmonary thromboembolism development in COVID-19.

BACKGROUND: Since the emergence of coronavirus disease 2019 (COVID-19), various clinical manifestations ranging from asymptomatic to severe, life-threatening courses have been presented. It is well known that COVID-19 patients are at an increased risk of pulmonary thromboembolism (PTE) development; however, the associated demographic, medical, and clinical factors for developing PTE remain unknown. The current study aimed to assess the characteristics of patients with PTE. METHODS: This case-control study was derived from an ongoing population-based investigation of hospitalized patients with COVID-19 pneumonia. The case group included 99 patients with PTE confirmed by computed tomography pulmonary angiography (CTPA), and the controls (N=132) were age-matched patients selected from the PTE-suspected patients with a negative CTPA. The demographic, medical, and clinical characteristics of the study population were entered into the study checklist and compared. A logistic regression test was used to determine the factors associated with PTE development. RESULTS: Among the 13,099 admitted patients, 690 (5.26%) were suspected of having PTE according to their clinical manifestations. CTPA was performed for suspected cases, and PTE was confirmed in 132 patients (19.13%). Logistic regression assessments revealed that male gender (OR, 2.39; 95%CI, 1.38‒4.13), decreased oxygen saturation (OR, 2.33; 95%CI, 1.27‒4.26), and lower hemoglobin (OR, 0.83, 0.95), and albumin (OR, 0.31; 95%CI, 0.18‒0.53) levels were associated with PTE development. CONCLUSION: PTE was confirmed in one-fifth of suspected patients who underwent CTPA imaging. Male sex, decreased oxygen saturation, and lower levels of hemoglobin and albumin were independent predictors of PTE in patients with COVID-19 pneumonia.

Comparative Evaluation between the LaxaPlus Barij® and Polyethylene Glycol (4000) in the Pediatric Functional Constipation in Children 2-15 Years Old.

Objective: This study aimed to compare the LaxaPlus Barij® and polyethylene glycol (4000) in pediatric (children 2-15 years old) functional constipation. Methods: The present study is a randomized clinical trial. The study population included patients with functional constipation aged 2-15 years who were referred to the gastrointestinal clinic of Imam Hossein hospital in Isfahan in 2019. Patients were randomly assigned into two treatment groups. Data analysis was performed using SPSS software. The significance level in the present study is considered <0.05. Findings: Sixty children with functional constipation were selected based on the inclusion and exclusion criteria in this study. The present study results showed no significant difference between demographic characteristics, including age, weight, and gender of children with constipation in the two groups (P > 0.05). The present study results showed that both groups' mean stool consistency and the number of bowel movements increased significantly after the intervention (P < 0.05). However, the number of bowel movements in the first group was significantly higher than in the second group (P < 0.05). Conclusion: The present study results showed that both drugs effectively treat children with functional constipation. However, after 8 weeks of intervention, the frequency of bowel movements, pain intensity, and abdominal pain in the group LaxaPlus Barij® was more effective. However, the level of satisfaction did not differ significantly between the two groups.

Comparing the Effect of a Herbal-based Laxative (Goleghand®) and Polyethylene Glycol on Functional Constipation among Children: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effectiveness, safety, and document the reported adverse effect of a herbal-based laxative (Goleghand®) for the maintenance treatment of functional constipation in young children. METHODS: We conducted a randomized clinical trial from April 2019 to September 2020. Children aged 2-15 years with functional constipation defined according to the Rome IV criteria were eligible for study inclusion. Eligible children were randomly allocated to receive polyethylene glycol (PEG) or Goleghand®. The number and consistency of stools per day, painful defecation, abdominal pain, and fecal incontinence were reported weekly by parents. The statistical analyses were performed by determining means and standard deviations, t-test, Chi-square test, ANOVA repeated measures, and Fisher's exact test, with significance, accepted at the 5% level. FINDINGS: Sixty patients have been enrolled in the study. Parental satisfaction scores did not change significantly in either group or over the follow-up period. Our results showed that the effect of time (P < 0.001) and also the effect of group type (P = 0.01) on the number of fecal defecations was significant. The mean number of defecations increased first and then decreased significantly over time, but this decrease was more significant in the PEG group than in the Goleghand® group (P = 0.001). Furthermore, the effect of time on the fecal consistency score was significant (P = 0.047). The mean score of fecal consistency in both groups decreased over time. CONCLUSION: Goleghand® was similar in efficacy to PEG for 8 weeks of pediatric functional constipation treatment in this randomized clinical trial. Goleghand® can be considered as a new herbal laxative drug for pediatric functional constipation.

Therapy with new generation of biodegradable and bioconjugate 3D printed artificial gastrointestinal lumen.

OBJECTIVES: Many patients die due to vascular, gastrointestinal lumen problems, and coronary heart diseases. Synthetic vessels that are made of biodegradable-nanofiber polymers have significant properties such as proper biodegradability and efficient physical properties such as high strength and flexibility. Some of the best options for supporting cells in soft tissue engineering and design are applications of thermoplastic polyurethane polymer in the venous tissue. In this study, the first nanoparticle-reinforced polymeric artificial prosthesis was designed and tested to be used in the human body. MATERIALS AND METHODS: In this study, artificial gastrointestinal lumen were fabricated and prepared using a 3D printer. To improve cell adhesion, wettability properties and mechanical stability of elastin biopolymer with magnetic nanoparticles (MNPs) as well as single-walled carbon nanotubes (SWCNT) were prepared as separate filaments. MNPs were made in 5-7 mm sizes and then examined for mechanical, biological, and hyperthermia properties. Then, the obtained results of the gastrointestinal lumen were simulated using the Abaqus software package with a three-branch. The results were evaluated by X-ray diffraction (XRD) and scanning electron microscopy (SEM) for morphology and phase analysis. RESULTS: The obtained results of the designed vessels showed remarkable improvement in mechanical properties of the SWCNT vessels and hyperthermia properties of the vessels containing the MNPs. The results of computational fluid dynamics (CFD) analysis showed that the artificial vessels had lower shear stress at the output. CONCLUSION: Five-mm MNP containing vessels showed noticeable chemical and biological properties along with ideal magnetic results in the treatment of thrombosis and vascular obstruction.

Review of COVID-19 Treatment.

Many contagious diseases, such as plague or cholera, played a role in changing the pathway of history. In this respect, although coronavirus was not as dangerous as novel diseases such as swine flu and Ebola, the spread and the power of coronavirus infiltration caused public fear across the world. Three viruses among coronaviruses have been epidemic during the recent years, including severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 or new coronavirus. Respiratory droplets transmit the coronavirus through direct and indirect contact, and it can be transmitted through the contact in the case of remaining, the infected person's secretion on the surface. Based on the conducted studies on the treatment of COVID-19 disease, there is virtually no cure or vaccine for coronavirus infections yet. Those infected with Covid 19 are quarantined to prevent the outbreak of this disease. However, the researchers carried out different studies to investigate the impact of the various drugs on this virus, which in this study, we will examine the outline of this disease and the other conducted studies.

Comparison of Comfort and Effectiveness of Total Face Mask and Oronasal Mask in Noninvasive Positive Pressure Ventilation in Patients with Acute Respiratory Failure: A Clinical Trial.

Background. There is a growing controversy about the use of oronasal masks (ONM) or total facemask (TFM) in noninvasive positive pressure ventilation (NPPV), so we designed a trial to compare the uses of these two masks in terms of effectiveness and comfort. Methods. Between February and November 2014, a total of 48 patients with respiratory failure were studied. Patients were randomized to receive NPPV via ONM or TFM. Data were recorded at 60 minutes and six and 24 hours after intervention. Patient comfort was assessed using a questionnaire. Data were analyzed using t-test and chi-square test. Repeated measures ANOVA and Mann-Whitney U test were used to compare clinical and laboratory data. Results. There were no differences in venous blood gas (VBG) values between the two groups (P > 0.05). However, at six hours, TFM was much more effective in reducing the partial pressure of carbon dioxide (PCO2) (P = 0.04). Patient comfort and acceptance were statistically similar in both groups (P > 0.05). Total time of NPPV was also similar in the two groups (P > 0.05). Conclusions. TFM was superior to ONM in acute phase of respiratory failure but not once the patients were out of acute phase.

Simultaneous Presentation of Wilson's Disease and Autoimmune Hepatitis; A Case Report and Review of Literature.

INTRODUCTION: Coexistence of Wilson's disease and autoimmune hepatitis has been rarely reported in English literature. In this group of patients, there exist features of both diseases and laboratory and histopathological studies may be misleading. Medical treatment for any of these entities, per se, may result in poor response. Therefore, by considering the acute hepatitis resembling Wilson's disease and autoimmune hepatitis, simultaneous therapy with immunosuppressive and penicillamine may have a superior benefit. CASE PRESENTATION: We present the case of a 10-year-old boy with nausea, vomiting, yellowish discoloration of skin and sclera, abdominal pain and tea-color urine. Physical examination showed mild hepatomegaly and right upper quadrant tenderness. Laboratory and histochemical studies and atomic absorption test were done and the results were highly suggestive of both Wilson's disease and autoimmune hepatitis, in him. CONCLUSIONS: This case study highlights, although rare, the coexistence of Wilson's disease and autoimmune hepatitis and the need to maintain a high level of awareness of this problem. Therefore, it is reasonable to consider this type of hepatitis in rare patients, with dominant features of both diseases at the same time.