Clinical, Immunological, and Genetic Findings in Iranian Patients with MHC-II Deficiency: Confirmation of c.162delG RFXANK Founder Mutation in the Iranian Population.

PURPOSE: Major histocompatibility complex class II (MHC-II) deficiency is a rare inborn error of immunity (IEI). Impaired antigen presentation to CD4 + T cells results in combined immunodeficiency (CID). Patients typically present with severe respiratory and gastrointestinal tract infections at early ages. Hematopoietic stem cell transplantation (HSCT) is the only curative therapy. METHODS: We describe the clinical, immunologic, and genetic features of eighteen unrelated Iranian patients with MHC-II deficiency. RESULTS: Consanguinity was present in all affected families. The median age at the initial presentation was 5.5 months (range 7 days to 18 years). The main symptoms included failure to thrive, persistent diarrhea, and pneumonia. Autoimmune and neurologic features were also documented in about one-third of the patients, respectively. Thirteen patients carried RFXANK gene mutations, two carried RFX5 gene mutations, and three carried a RFXAP gene mutation. Six patients shared the same RFXANK founder mutation (c.162delG); limited to the Iranian population and dated to approximately 1296 years ago. Four of the patients underwent HSCT; three of them are alive. On the other hand, nine of the fourteen patients who did not undergo HSCT had a poor prognosis and died. CONCLUSION: MHC-II deficiency is not rare in Iran, with a high rate of consanguinity. It should be considered in the differential diagnosis of CID at any age. With the limited access to HSCT and its variable results in MHC-II deficiency, implementing genetic counseling and family planning for the affected families are mandatory. We are better determined to study the c.162delG RFXANK heterozygous mutation frequency in the Iranian population.

Management of Intractable Functional Constipation in Children by Interferential Therapy: Transabdominal or Pelvic Floor.

BACKGROUND: To compare the effectiveness of pelvic floor interferential (IF) therapy with trans-abdominal IF therapy in children with intractable functional constipation. METHODS: Information of 64 children (38 boys, 26 girls; mean age: 6.6 ± 2.2) with functional constipation who had been treated with IF therapy were considered for this retrospective study. Group A (n = 32) underwent pelvic IF electrical stimulation + pelvic floor muscle (PFM) exercises while the group B (n = 32) received transabdominal IF therapy + PFM exercises. A complete bowel habit diary, a constipation score questionnaire and a seeable pain scores had been recorded before, after the ending of treatment courses and six months later for children in both groups. Additionally, children had been assessed with a constipation-related quality of life questionnaire before and six months after treatment. RESULTS: The number of patients who compiled the diagnostic criteria for constipation significantly decreased in both groups after treatment, in which 27/32 (84.3%) of patients in each group had no constipation after the ending of therapy courses (P = 1). Fecal soiling episodes reduced in both groups after treatment, this finding was significantly higher in group A than in group B after the ending of therapy courses (P = 0.05) and six months later (P = 0.01). CONCLUSION: Results of this study showed that using IF therapy both pelvic floor and transabdominal significantly boosts the effects of treatment among patients with functional constipation. Pelvic floor IF therapy is more effective in patients who had concomitant fecal soiling.

Effect of helicobacter pylori infection eradication on serum level of anti-tissue transglutaminase in children with celiac disease.

BACKGROUND: Evidence shows the increase of anti-tissue transglutaminase (tTG) levels in various conditions, including infectious agents, independently of celiac disease (CD). The aim of this study was to investigate the effect of helicobacter pylori (H.pylori) infection eradication on serum level of tTG in children with CD. METHODS: This study was conducted on children aged 2 to 18 who referred to reference hospitals for diagnosis of CD. After upper endoscopy and biopsy to confirm CD and H.pylori infection, the children were divided into three groups (including group one: 16 CD patients with positive H. pylori; group two: 16 non-CD patients with positive H. pylori; and group three: 56 CD patients with negative H. pylori), respectively. The tTG level in study groups were compared after the eradication of H.pylori. RESULTS: The mean age of the subjects in the group one, two, and three was 9.7 ± 3.33, 11.8 ± 3.14, and 7.6 ± 3.32 years, respectively. Our results showed that in group one, mean tTG increased after eradication of H.pylori infection, however, these changes were not significant (182.43 vs. 157.18, P = 0.121). In the second group, although unlike the first group, mean tTG decreased after eradication of the infection, but still these changes were not significant (9.56 vs. 22.18, P = 0.449). Furthermore, at the baseline level, the mean tTG in the group three was closer to the mean tTG in the first group. CONCLUSION: Our findings showed that the eradication of H.pylori infection does not have a significant effect on tTG levels in children with and without CD.

Esophageal Stents for the Management of Benign Esophageal Strictures in Children and Adolescents: A Systematic Review of Observational Studies.

Little is known about the efficacy and safety of esophageal stents for the management of esophageal strictures in children and adolescents. A systematic review was performed to assess the efficacy and safety of esophageal stents for the management of benign esophageal strictures in children and adolescents. Observational studies related to the examination of esophageal stents in pediatrics were extracted using the original databases by December 2021. We found 18 retrospective and prospective studies with a total of 340 children and adolescents. Overall, our findings show that different therapeutic modalities based on esophageal stents were offered to children and adolescents for various indications, in which most studies reported successful cases, although ineffective claims cannot be ignored. Fully covered self-expandable metal stent, self-expandable metal stent, and silastic esophageal stent were the stent types most used, although different materials and prototypes were reported as well. The number of stents used per patient and the duration of the stenting therapy varied widely (ranging from 1 to 584 days). Such treatments were not standardized because of different factors, such as different tolerance to complications in subjects aged 1 month and 16 years, frequent stent migration requiring removal followed or not by its replacement, different guides provided by each stent manufacturer, and successful healing of esophageal lesions. Different esophageal stents may be a reasonable therapeutic approach for the management of benign esophageal strictures in children and adolescents. We believe that esophagus-sparing methods like stents represent a promising alternative or adjunctive treatment to be considered in pediatrics.

Comparative Efficacy of Transcutaneous Functional Electrical Stimulation With or Without Biofeedback Therapy on Functional Non-retentive Fecal Incontinence in Children: A Randomized Clinical Trial.

BACKGROUND: We compared the effects of transcutaneous functional electrical stimulation (TFES) and biofeedback therapy with TFES alone in a cohort of children with functional non-retentive fecal incontinence (FNRFI). METHODS: This prospective, single-center randomized clinical trial was performed on 40 children with FNRFI. Patients were randomly allocated into two equal treatment groups. Group A (n = 20) underwent TFES + biofeedback therapy, and group B (n = 20) received TFES alone. All patients were assessed with a pediatric fecal incontinence (FI) score questionnaire, a visual pain score, and a bowel habit diary both before and at the end of treatment sessions and also at 6 months of follow-up. In addition, a FI quality-of-life (QoL) questionnaire was recorded for all patients before and 6 months after the treatment. RESULTS: FI significantly improved in 13/20 (65%) patients in group A and 11/20 (55%) patients in group B (P < 0.05). A significant reduction in FI score was seen in each group at the end of treatment sessions and maintained at 6 months of follow-up (P < 0.05). A significant improvement in FI-QoL scores was seen in both groups at 6 months of follow-up in which there was no significant difference in terms of FI-QoL scores improvement between both groups after treatment. CONCLUSIONS: The use of electrical stimulation in combination with other treatment methods improves symptoms in patients with FNRFI who are refractory to conventional treatment.

Acute pancreatitis in 60 Iranian children: do pediatricians follow the new guidelines in diagnosis and management of acute pancreatitis?

BACKGROUND: The incidence of acute pancreatitis in children is increasing, but causes and diagnostic and therapeutic methods are various in different centers. The aim of this study was to investigate the common causes and routine diagnostic and therapeutic methods of acute pancreatitis in children in a pediatric gastrointestinal referral center and its accordance with existing guidelines. METHODS: In this retrospective, cross-sectional study, a total of 60 children with a diagnosis of acute pancreatitis, were studied. RESULTS: The most common causes of acute pancreatitis were systemic and metabolic diseases and medications. CT scan was performed for 36% of patients, but 31% of patients, for whom a CT scan was performed had no clear indication of CT scan. Only half of the patients received fluid 1.5 times their maintenance in the first 24 h. Antibiotic therapy was performed for 48% of patients but medical indications for antibiotic treatment were found in only 34% of cases. During the COVID-19 pandemic, the relative incidence of acute pancreatitis was increased. CONCLUSIONS: In children with systemic and metabolic disease and using anticonvulsant drugs, it is important to consider the incidence of this disease. In clinical education, the risks of radiation due to unnecessary CT scans and inappropriate prescription of antibiotics need to be emphasized. More research should be done to study the association between COVID-19 and acute pancreatitis.

Serum matrix metalloproteinase-7 levels in infants with cholestasis and biliary atresia.

BACKGROUND: The aim of this study was to evaluate the serum level of matrix metalloproteinase 7 (MMP7) in infants with cholestasis and the diagnostic values of this biomarker to differentiate biliary atresia (BA) from other causes of cholestasis. METHODS: This multi-center study is conducted during 2 years in Mofid children's hospital and Children's Medical Center, Pediatrics Center of Excellence Tehran, Iran. 54 infants with cholestasis were enrolled in this study with a control group consists of 41 healthy infants with the same age. Serum samples were taken from all these patients to assess serum levels of MMP7, Gamma-glutamyl Transferase (GGT). For each biomarker, we calculated the sensitivity and specificity and other statistical characteristics. RESULTS: There were 89 subjects, 22 patients with BA, 32 patients with non-BA cholestasis and 41 subjects as control group. The mean serum MMP7 levels in BA, non-BA cholestasis and control group was 15.91 ng/ml ± 6.64, 4.73 ng/ml ± 2.59 and 0.49 ng/ml ± 0.33, respectively. The best cut-off point is calculated 7.8 ng/ml for MMP7 and 434.5 U/L for GGT. The area under curve (AUC) for these two markers are 0.988 ± 0.008 and 0.854 ± 0.052, respectively. The sensitivity and specificity of MMP7 to differentiate biliary atresia from nonbiliary atresia cholestasis in our study was 95.5% and 94.5%, respectively. The sensitivity and specificity of GGT was 77.3% and 77.8%, respectively. These results show that the MMP7 has more sensitivity and specificity in differentiation. CONCLUSION: MMP7 demonstrated good accuracy to differentiate biliary atresia from other causes of cholestasis.

Non-retentive faecal incontinence in children: Conventional therapy alone or combined electrical stimulation.

AIMS: To compare the effects of functional electrical stimulation (FES) with conventional therapy and conventional therapy alone on improvement of faecal incontinence (FI) symptoms in a number of children with functional non-retentive FI. METHODS: Data of 28 children with FI were accepted for this retrospective study. The case group (n = 14) underwent FES + conventional therapy and the control group (n = 14) received conventional therapy only. Data of children with faecal retention, inflammatory, anatomic, metabolic and neurological disorders were excluded. Children were assessed with a paediatric FI score questionnaire, and a bowel habit diary both before treatment sessions, after they ended, and after 6 months. A FI quality of life questionnaire was completed before and after treatment for all children. RESULTS: Full response to the treatment (100% reduction in FI episodes) was significantly observed in 8/14 (57.1%) of children in the case group compared to 2/14 (14.2%) of children in the control group after the ending of treatment sessions (P = 0.005). The baseline mean ± SD of FI episodes per week was 3.7 ± 2.1 among both groups which significantly decreased after the ending of treatment sessions in the case group compared to the control group (1.4 ± 2.1 vs 3 ± 2.7; P = 0.05). Mean ± SD of FI score was significantly reduced in the case group compared to the controls after the ending of treatment sessions (3.9 ± 4.5 vs 8 ± 4.7; P = 0.02) and maintained after 6 months (P = 0.05). CONCLUSIONS: Functional electrical stimulation is a safe, effective, non-invasive, inexpensive, reproducible and easy-to-use modality for treatment of functional non-retentive faecal incintinence in children.

Juvenile Polyps with Osseous Metaplasia: Report of Two Pediatric Cases and Review of the Literature.

BACKGROUND: Osseous metaplasia is considered as a response to insults such as chronic inflammation or mucin extravasation in colorectal polyps. CASE REPORT: we report two cases of osseous metaplasia in juvenile (retention) polyps as incidental histopathological findings in a case of rectal juvenile polyposis and a patient with solitary rectal juvenile polyp. CONCLUSION: Osseous metaplasia can occur in colorectal juvenile polyps and is considered a probable response to mucin extravasation and/or chronic inflammation. The clinical and prognostic significance of osseous metaplasia in these polyps is unknown.

Intrarectal Electromotive Botulinum Toxin Type A Administration in Children With Intractable Constipation: A Randomized Clinical Trial.

INTRODUCTION: Children with refractory constipation might not respond to conventional medical treatments. In this study, we assessed the effectiveness of intrarectal botulinum toxin type A/electromotive drug administration (BoNTA/EMDA) on constipation in these children and compared its efficacy with routine intrasphincteric BoNTA injection. METHODS: From 2017 to 2019, 60 children aged 5-13 years who fulfilled Rome III criteria for intractable constipation were enrolled and randomly assigned into 2 treatment groups. EMDA group (n = 30) underwent BoNTA/EMDA, whereas the control group (n = 30) received injection of BoNTA into the internal anal sphincter. A complete bowel habit diary (with data on the frequency of defecation per week, stool form, and the number of fecal soiling episodes), a constipation score questionnaire, and a visual pain score were recorded before treatment and at 1 month and 6 months after treatment. In addition, children in both groups were assessed with a constipation-related quality of life questionnaire. RESULTS: After 1-month follow-up, treatment reduced the number of patients fulfilling the diagnostic criteria in both EMDA (24/30, 80%) and injection (25/30, 83.3%) groups (P < 0.001). The stool form was normalized in 73.3% (22/30) in EMDA group and 80% (24/30) in injection group after treatment. The median of constipation score and pain score decreased significantly in both groups after treatment (P < 0.001 and P < 0.001, respectively). DISCUSSION: BoNTA/EMDA seems to be as effective as intrasphincteric BoNTA injection for treatment of intractable constipation. In addition, this technique is associated with less comorbidity, is less costly, and can be performed in an office-based setting without general anesthesia.

Effects of Interferential Electrical Stimulation Plus Pelvic Floor Muscles Exercises on Functional Constipation in Children: A Randomized Clinical Trial.

OBJECTIVES: Functional constipation is a common condition in children. We assessed the effectiveness of combined interferential (IF) electrical stimulation and pelvic floor muscle (PFM) exercises on functional constipation in children. METHODS: We conducted a single-center, double-blind randomized clinical trial study during 2014-2017 in Tehran, Iran. Ninety children, aged 5-13 years, who fulfilled Rome III criteria were enrolled and randomly assigned into two treatment groups. Case group (n=45) underwent IF electrical stimulation and PFM exercises, whereas the control group (n=45) received PFM exercises plus sham stimulation. A complete bowel habit diary (with concerning data on the frequency of defecation per week, stool form, and the number of fecal soiling episodes), a constipation score questionnaire, and a visual pain score were recorded before, after the treatment and 6 months later for all participants. In addition, children in both groups were assessed with a constipation-related quality-of-life questionnaire before, after the end of treatment sessions, and 6 months after the treatment. RESULTS: Treatment success was achieved for 88.4% of children in the case group compared with 43.2% of children in the control group after the treatment (P<0.003). The median constipation score was reduced in both groups, with the cases having significantly lower scores after the treatment (4 vs. 8, P<0.000). Stool form normalized in 75.6% of the cases and 45.5% of the controls after the treatment (P<0.01). CONCLUSIONS: Our results showed that using IF electrical stimulation as an adjuvant therapy to the medical and rehabilitation programs significantly boosts the effects of treatment among these patients.

Clinical Phenotype and Disease Course of Inflammatory Bowel Disease in Iran: Results of the Iranian Registry of Crohn's and Colitis (IRCC).

BACKGROUND: Data on the epidemiology of inflammatory bowel disease (IBD) in the Middle East are scarce. We aimed to describe the clinical phenotype, disease course, and medication usage of IBD cases from Iran in the Middle East. METHODS: We conducted a cross-sectional study of registered IBD patients in the Iranian Registry of Crohn's and Colitis (IRCC) from 2017 until 2022. We collected information on demographic characteristics, past medical history, family history, disease extent and location, extra-intestinal manifestations, IBD medications, and activity using the IBD-control-8 questionnaire and the Manitoba IBD index, admissions history, history of colon cancer, and IBD-related surgeries. RESULTS: In total, 9746 patients with ulcerative colitis (UC) (n=7793), and Crohn's disease (CD) (n=1953) were reported. The UC to CD ratio was 3.99. The median age at diagnosis was 29.2 (IQR: 22.6,37.6) and 27.6 (IQR: 20.6,37.6) for patients with UC and CD, respectively. The male-to-female ratio was 1.28 in CD patients. A positive family history was observed in 17.9% of UC patients. The majority of UC patients had pancolitis (47%). Ileocolonic involvement was the most common type of involvement in CD patients (43.7%), and the prevalence of stricturing behavior was 4.6%. A prevalence of 0.3% was observed for colorectal cancer among patients with UC. Moreover,15.2% of UC patients and 38.4% of CD patients had been treated with anti-tumor necrosis factor (anti-TNF). CONCLUSION: In this national registry-based study, there are significant differences in some clinical phenotypes such as the prevalence of extra-intestinal manifestations and treatment strategies such as biological use in different geographical locations.

A quick algorithmic review on management of viral infectious diseases in pediatric solid organ transplant recipients.

Pediatric solid organ transplant is a life-saving procedure for children with end-stage organ failure. Viral infections are a common complication following pediatric solid organ transplantation (SOT), which can lead to increased morbidity and mortality. Pediatric solid organ transplant recipients are at an increased risk of viral infections due to their immunosuppressed state. The most commonly encountered viruses include cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus (HSV), varicella-zoster virus (VZV), adenoviruses, and BK polyomavirus. Prevention strategies include vaccination prior to transplantation, post-transplant prophylaxis with antiviral agents, and preemptive therapy. Treatment options vary depending on the virus and may include antiviral therapy and sometimes immunosuppression modification. This review provides a Quick Algorithmic overview of prevention and treatment strategies for viral infectious diseases in pediatric solid organ transplant recipient.

Vitamin D therapy in pediatric patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND: There is some evidence for the role of vitamin D deficiency in the pathogenesis of inflammatory bowel disease (IBD) in the pediatric population. However, the results are contradictory. Therefore, we have conducted a systematic review and meta-analysis to evaluated the effect of vitamin D on pediatric patients with IBD. METHODS: We carried out a systematic search in databases from inception until 20 January 2022. We included all relevant articles that evaluate the efficacy and safety of vitamin D on disease activity, inflammatory factors, and vitamin D and calcium levels in pediatric patients with IBD. Random effects models were used to combine the data. The main outcomes were then analyzed using weight mean difference (WMD) and respective 95% confidence interval (CI). RESULTS: Fifteen treatment arms met the eligibility criteria and were included. Pooled estimates indicated that intervention with vitamin D has a significantly beneficial effect on 25-hydroxyvitamin D3 [25(OH) D3] (pooled WMD of 17.662 ng/mL; CI 9.77-25.46; P < 0.001), calcium (pooled WMD of 0.17 mg/dL; CI 0.04-0.30; P = 0.009), and inflammatory factors including C-reactive protein (CRP) (pooled WMD of -6.57 mg/L; CI -11.47 to -1.67; P = 0.009) and erythrocyte sedimentation rate (ESR) (pooled WMD of -7.94 mm/h; CI -12.65 to -3.22; P = 0.001) levels. In addition, this effect was greater for vitamin D levels at doses greater than 2000 IU, and when follow-up duration was more than 12 weeks. CONCLUSION: This study showed that vitamin D therapy can have a significant and beneficial effect on 25(OH) D3, calcium, and inflammatory factors in children and adolescents with IBD.

Association of fecal calprotectin level with eosinophilic gastrointestinal disease in Iranian pediatrics.

INTRODUCTION: Fecal calprotectin (FC) is a noninvasive biomarker for assessing the inflammatory status of the gastrointestinal tract. The aim of this study was to determine the association between FC levels and Eosinophilic colitis (EC) before and after treatment in pediatrics. METHOD: In this cross-sectional study, 330 patients with rectorrhagia and FC levels > 200 µg/g were included in the study. Patients were then subjected to colonoscopy, and if 30 or more eosinophils were observed in the pathology of at least two parts of the colon, EC was diagnosed. Of the 330 patients included in the study, 14 patients were diagnosed as EC. Treatment included seven food elimination diet (food allergens) for 3 months. After 3 months, FC levels were repeated and colonoscopy was performed. RESULTS: The mean age of the children was 5.9 years. After the elimination diet, the number of eosinophils in all segments of colon significantly decreased (P < 0.001) and according to the pathology report, the number of eosinophils improved in 42.9% of patients. Also, the mean number of segments involved in the colon of patients was significantly decreased (P < 0.001). Mean FC levels were significantly decreased after 3 months (P < 0.001). The cut-off point of 114 µg/g of FC had sensitivity (75%), specificity (67%), positive predictive value (75%), negative predictive value (67%), accuracy (71.4%), and area under the ROC curve (0.708) acceptable in predicting EC. CONCLUSION: This study showed that FC levels can be elevated in patients with EC, which is easily corrected with a targeted elimination of food allergens.

Cerebrovascular Events in Pediatric Inflammatory Bowel Disease: A Review of Published Cases.

Pediatric inflammatory bowel disease (PIBD) is a multisystem disorder characterized by intestinal and extraintestinal manifestations and complications. Cerebrovascular events (CVE) are rare extraintestinal complications in patients with PIBD. Statistics show that 3.3% patients with PIBD and 1.3-6.4% adult patients with inflammatory bowel disease (IBD) experience CVE during the course of the disease. Therefore, this study aimed to review the records of children with IBD who developed CVE during the course of the disease. We retrospectively reviewed 62 cases of PIBD complicated by CVE. The mean patient age at the time of thrombotic events was 12.48±4.13 years. The incidence of ulcerative colitis was significantly higher than that of Crohn's disease (43 [70.5%] vs. 13 [21.3%] patients). Most patients (87.93%) were in the active phase of IBD at the time of CVE. The mean time interval between the onset of IBD and CVE was 20.84 weeks. Overall, 11 (26.83%) patients showed neurological symptoms of CVE at disease onset. The most frequent symptom on admission was persistent and severe headaches (67.85%). The most common site of cerebral venous thrombosis was the transverse sinuses (n=23, 53.48%). The right middle cerebral artery (n=3, 33.34%) was the predominant site of cerebral arterial infarction. Overall, 41 (69.49%) patients who were mostly administered unfractionated heparin or low-molecular-weight heparin (56.09%) recovered completely. Patients with IBD are at a risk of thromboembolism. CVE may be the most common type of thromboembolism. Based on these findings, the most common risk factor for CVE is IBD flares. In patients with CVE, anticoagulant therapy with heparin, followed by warfarin, is necessary.

Meta-analysis: efficacy of exclusive enteral nutrition as induction therapy on disease activity index, inflammation and growth factors in paediatric Crohn's disease.

BACKGROUND: There is evidence of inconsistency in sequelae of exclusive enteral nutrition (EEN) as induction therapy in paediatric patients with Crohn's disease (CD). AIM: To investigate the potential effects of EEN on paediatric Crohn's disease activity index (PCDAI), inflammation and biochemical parameters in paediatric patients with CD. METHODS: We performed a comprehensive systematic search of PubMed/MEDLINE, Web of Science, SCOPUS and Embase until 8 January 2022 regardless of the time of publication or language. Random-effects model was applied to combine the datasets. The main outcomes were analysed through mean difference (MD) and its 95% confidence interval (CI). RESULTS: Forty six studies met eligibility criteria and were included in the meta-analysis. Pooled findings indicated that PCDAI score (MD of -27.24; 95% CI -31.84 to -22.64), calprotectin (MD of -842.83 mg/kg; CI -1018.24 to -667.42), CRP (pooled MD of -2.36 mg/dl; CI -2.68 to -2.03), and ESR (MD of -21.09 mm/h; CI -23.79 to -18.38), albumin (MD of 0.65 g/dl; CI 0.58 to 0.72), haemoglobin (MD of 1.12 g/dl; CI 0.87 to 1.37), weight (MD of 4.30 kg; CI 3.39 to 5.22), and height (MD of 0.98 cm; CI 0.35 to 1.62) improved significantly with EEN. CONCLUSIONS: Adherence to EEN can have significant, beneficial effects as induction therapy in paediatric patients with CD.

Withdrawal Notice: MMR Vaccine Susceptibility of Viral Agents Causing Meningitis and Meningoencephalitis in Children

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