Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Enhanced Collagen Deposition in the Duodenum of Patients with Hyaline Fibromatosis Syndrome and Protein Losing Enteropathy.

Hyaline fibromatosis syndrome (HFS), resulting from ANTXR2 mutations, is an ultra-rare disease that causes intestinal lymphangiectasia and protein-losing enteropathy (PLE). The mechanisms leading to the gastrointestinal phenotype in these patients are not well defined. We present two patients with congenital diarrhea, severe PLE and unique clinical features resulting from deleterious ANTXR2 mutations. Intestinal organoids were generated from one of the patients, along with CRISPR-Cas9 ANTXR2 knockout, and compared with organoids from two healthy controls. The ANTXR2-deficient organoids displayed normal growth and polarity, compared to controls. Using an anthrax-toxin assay we showed that the c.155C>T mutation causes loss-of-function of ANTXR2 protein. An intrinsic defect of monolayer formation in patient-derived or ANTXR2KO organoids was not apparent, suggesting normal epithelial function. However, electron microscopy and second harmonic generation imaging showed abnormal collagen deposition in duodenal samples of these patients. Specifically, collagen VI, which is known to bind ANTXR2, was highly expressed in the duodenum of these patients. In conclusion, despite resistance to anthrax-toxin, epithelial cell function, and specifically monolayer formation, is intact in patients with HFS. Nevertheless, loss of ANTXR2-mediated signaling leads to collagen VI accumulation in the duodenum and abnormal extracellular matrix composition, which likely plays a role in development of PLE.

Quality-of-life Evaluation of Healthy Siblings of Children with Chronic Illness

Background: Chronic disease of children can cause changes in the health-related quality of life (HrQoL) of the family members. Aims: To evaluate the HrQoL of healthy siblings of children with chronic disease. Study Design: Cross-sectional study. Methods: The study included healthy sibling of children with chronic disease (cerebral palsy, epilepsy, diabetes, celiac disease, hematologic/oncologic disease, or asthma) and healthy sibling of healthy children to evaluate the quality of life. We used the Pediatric Quality of Life Inventory questionnaire; the physical health and psychosocial health scores were calculated using the responses of the sibling and parent. The primary endpoint was the comparison of HrQoL scores of healthy siblings of children with chronic disease and that of healthy siblings of healthy children. Results: This study included a respective healthy sibling of 191 children with chronic disease and healthy sibling of 100 healthy children. The physical health, psychosocial health, and total health scores of healthy siblings of children with chronic disease were significantly lower than that of healthy siblings of healthy children (p<0.001). Among the healthy siblings of children with chronic disease, the lowest psychosocial health score was found in the siblings of children with cerebral palsy, hematologic/oncologic disease, and asthma (p<0.001). The global impact on the quality of life for healthy siblings of children with chronic disease was significantly higher in the self-report of the children than that of the parents (30.4% versus 15.1%, p<0.05). Conclusion: Most healthy siblings of children with chronic disease are physically and psychosocially affected and there is low parental awareness of this condition. This can increase the risk of emotional neglect and abuse of these children. Therefore, special support programs are needed for the families of children with chronic diseases.

Lactobacillus reuteri DSM 17938 shortens acute infectious diarrhea in a pediatric outpatient setting / O Lactobacillus reuteri DSM 17938 reduz a diarreia infecciosa aguda no cuidado pediátrico ambulatorial

OBJECTIVE: Two randomized controlled clinical trials have shown thatLactobacillus (L) reuteri DSM 17938 reduces the duration of diarrhea in children hospitalized due to acute infectious diarrhea. This was the first trial evaluating the efficacy of L. reuteri DSM 17938 in outpatient children with acute infectious diarrhea.METHODS: This was a multicenter, randomized, single-blinded, case control clinical trial in children with acute watery diarrhea. A total of 64 children who presented at outpatient clinics were enrolled. The probiotic group received 1 × 108 CFU L. reuteri DSM 17938 for five days in addition to oral rehydration solution (ORS) and the second group was treated with ORS only. The primary endpoint was the duration of diarrhea (in hours). The secondary endpoint was the number of children with diarrhea at each day of the five days of intervention. Adverse events were also recorded.RESULTS: The mean duration of diarrhea was significantly reduced in the L. reuteri group compared to the control group (approximately 15 h, 60.4 ± 24.5 h [95% CI: 51.0-69.7 h] vs. 74.3 ± 15.3 h [95% CI: 68.7-79.9 h], p < 0.05). The percentage of children with diarrhea was lower in the L. reuteri group (13/29; 44.8%) after 48 h than the control group (27/31; 87%; RR: 0.51; 95% CI: 0.34-0.79,p < 0.01). From the 72nd hour of intervention onwards, there was no difference between the two groups in the percentage of children with diarrhea. No adverse effects related to L. reuteri were noted.CONCLUSION:L. reuteri DSM 17938 is effective, safe, and well-tolerated in outpatient children with acute infectious diarrhea.

OBJETIVO: Dois ensaios clínicos randomizados controlados demonstraram que oLactobacillus (L) reuteri DSM 17938 reduz a duração de diarreia em crianças hospitalizadas devido a diarreia infecciosa aguda. Este é o primeiro ensaio que avalia a eficácia do L. reuteri DSM 17938 em crianças com diarreia infecciosa aguda no ambulatório.MÉTODOS: Ensaio clínico multicêntrico, randomizado, único cego, com grupos paralelos e controlado em crianças com diarreia aguda. Foram inscritas 64 crianças internadas na clínica ambulatorial. O grupo probiótico recebeu 1 × 108 CFU L. reuteri DSM 17938 por cinco dias, além de uma solução de reidratação oral (SRO), e o segundo grupo foi tratado apenas com SRO. O desfecho principal foi a duração da diarreia (em horas). O desfecho secundário foi o número de crianças com diarreia em cada um dos cinco dias da intervenção. Os eventos adversos também foram registrados.RESULTADOS: A duração média da diarreia foi significativamente reduzida no grupoL. reuteri em comparação com o grupo de controle (aproximadamente 15 horas; 60,4 ± 24,5 horas [51,0-69,7 horas, IC de 95%] em comparação com 74,3 ± 15,3 horas [68,7-79,9 horas, IC de 95%], p < 0,05). O percentual de crianças com diarreia foi menor no grupo L. reuteri (13/29; 44,8%) após 48 horas do que no grupo de controle (27/31; 87%) (RR: 0,51; 0,34-0,79; IC de 95%, < 0,01). A partir da 72a hora de intervenção, não havia diferença entre os dois grupos no percentual de crianças com diarreia. Nenhum efeito adverso com relação ao L. reuteri foi observado.CONCLUSÃO: O L. reuteri DSM 17938 é eficaz, seguro e bem tolerado por crianças com diarreia infecciosa aguda no ambulatório.

Giant Condyloma Acuminate Due to Human Papillomavirus Type 16 in an Infant Successfully Treated with Topical Imiquimod Therapy.

Anogenital warts related to human papillomavirus (HPV) have been observed in children. Definition of the transmission mode, therapy, and follow-up for long term potential complications is important. A 27-month old girl was admitted with multiple pedunculated red-purple colored cauliflower-like lesions of 1.5 years duration. Clinical/histopathological and microbiological diagnosis was condyloma acuminate due to HPV type 16. After 12 weeks of imiquimod 5% cream application (pea-sized) overnight three times per week, the perianal warts had completely disappeared. The mode of transmission of HPV 16 in our case was probably horizontal, related to the sharing of common personal hygiene items in the women's shelter. We report herein the case of an infant living in a women's shelter with giant condyloma acuminata due to HPV 16, which was successfully treated with topical imiquimod therapy. This patient should be followed up for recurrence and potential malignant lesions related to HPV type 16.

The association of apoptotic protein expressions sensitive to apoptosis gene, p73 and p53 with the prognosis of cervical carcinoma.

OBJECTIVE: To evaluate the expressions of several apoptotic pathway proteins in relation to clinical parameters and survival in patients with cervical carcinoma. METHODS: A total of 20 patients with clinically advanced staged carcinoma of cervix (International Federation of Gynecology and Obstetrics [FIGO] stage IIB-IVA) aged from 40 to 75 years were included in this study. The expression profile of anti-apoptotic protein (sensitive to apoptosis gene [SAG]), mitochondrial apoptotic proteins (B-cell lymphoma-extra-large [Bcl-xL] and Bcl-2 homologous antagonist/killer [Bak]), and tumor suppressor proteins (p73 and p53) were examined by real-time polymerase chain reaction experiments along with their relation to clinical parameters and survival analyses during follow-up for 5 to 8 years. RESULTS: No significant difference was found in the expressions of SAG, Bcl-xL, Bak, p73 and p53 proteins with respect to stage and grade of tumor. A significant positive correlation was noted between SAG and Bcl-xL genes (r=0.752, P<0.001) and between SAG and Bak genes (r=0.589, P=0.006). Among genes determined to be significantly associated with overall survival in the univariate analysis (P=0.026 for SAG, P=0.002 for Bcl-xL, and P=0.027 for p53), only p53 was identified as the significant predictor in the multivariate analysis (hazard ratio: 8.53, 95% confidence interval: 1.34-54.2, P=0.023). CONCLUSION: In conclusion, our findings demonstrated a reverse correlation of SAG, Bcl-xL, and p53 expressions with overall survival of patients. No association of apoptotic pathway proteins with clinicopathological characteristics of cervical carcinoma patients was noted. Low SAG, Bcl-xL, and p53 expression levels revealed to be useful as prognostic predictors in patients with cervical carcinoma.

Clinical efficacy of Saccharomyces boulardii or metronidazole in symptomatic children with Blastocystis hominis infection.

Although many Blastocystis infections remain asymptomatic, recent data suggest it also causes frequent symptoms. Therapy should be limited to patients with persistent symptoms and a complete workup for alternative etiologies. The goal of this study was to compare the natural evolution (no treatment) to the efficacy of Saccharomyces boulardii (S. boulardii) or metronidazole for the duration of diarrhea and the duration of colonization in children with gastrointestinal symptoms and positive stool examination for Blastocystis hominis. This randomized single-blinded clinical trial included children presenting with gastrointestinal symptoms (abdominal pain, diarrhea, nausea-vomiting, flatulence) more than 2 weeks and confirmed B. hominis by stool examination (B. hominis cysts in the stool with microscopic examination of the fresh stool). The primary end points were clinical evaluation and result of microscopic stool examination at day 15. Secondary end points were the same end points at day 30. Randomization was performed by alternating inclusion: group A, S. boulardii (250 mg twice a day, Reflor®) during 10 days; group B, metronidazole (30 mg/kg twice daily) for 10 days; group C, no treatment. At day 15 and 30 after inclusion, the patients were re-evaluated, and stool samples were examined microscopically. On day 15, children that were still symptomatic and/or were still B. hominis-infected in group C were treated with metronidazole for 10 days. There was no statistically significant difference between the three study groups for age, gender, and the presence of diarrhea and abdominal pain. On day 15, clinical cure was observed in 77.7% in group A (n, 18); in 66.6% in group B (n, 15); and 40% in group C (n:15) (p < 0.031, between groups A and C). Disappearance of the cysts from the stools on day 15 was 80% in group B, 72.2% in group A, and 26.6% in group C (p = 0.011, between group B and group C; p = 0.013, between group A and group C). At the end of the first month after inclusion, clinical cure rate was 94.4% in group A and 73.3% in group B (p = 0.11). Parasitological cure rate for B. hominis was very comparable between both groups (94.4% vs. 93.3%, p = 0.43). Metronidazole or S. boulardii has potential beneficial effects in B. hominis infection (symptoms, presence of parasites). These findings challenge the actual guidelines.

Clinical efficacy of Saccharomyces boulardii and metronidazole compared to metronidazole alone in children with acute bloody diarrhea caused by amebiasis: a prospective, randomized, open label study.

The aim was to evaluate the efficacy of Saccharomyces boulardii (Sb) in addition to metronidazole in amebiasis. A prospective, randomized, open clinical trial was performed in 50 children presenting with acute bloody diarrhea caused by Entameba histolytica. Group A and B (each N = 25) was treated with metronidazole, but Sb (250 mg, twice daily) during the 7 days was added to Group B patients who were re-evaluated 2, 3, 5, 10, and 30 days after diagnosis. Duration of bloody diarrhea was significantly longer in Group A (72.0 +/- 28.5 versus 42.2 +/- 17.4 hours, P < 0.001). On day 5, amebic cysts had disappeared in all children in Group B, whereas in Group A, amebic cysts were still present in 6 children (P < 0.05). On day 10, all children were cured and cysts had disappeared in all. The addition of Sb to metronidazole in amebiasis significantly decreases duration of (bloody) diarrhea and enhances clearance of cysts.

Induction chemotherapy and chemoradiation therapy for inoperable locally advanced non-small-cell lung cancer: a single-institution review of two different regimens.

PURPOSE: We compared 2 different chemotherapeutic agents in combination with cisplatin as induction chemotherapy (ICT) followed by chemoradiation therapy (CHRT) in patients with inoperable locally advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: A total of 90 patients with inoperable locally advanced NSCLC received 3 courses of ICT consisting of gemcitabine 1200 mg/m2 on day 1 and day 8 every 3 weeks and cisplatin 75 mg/m2 on day 1 every 3 weeks (group 1; n = 39) or docetaxel 75 mg/m2 on day 1 every 3 weeks and cisplatin 75 mg/m2 on day 1 every 3 weeks (group 2; n = 51) followed by CHRT (docetaxel 30 mg/m2 every week and cisplatin 20 mg/m2 every week with 6600 cGy radiation therapy). RESULTS: After the ICT, the response rate for group 2 (88.2%) was significantly higher than that of the gemcitabine-cisplatin arm (64.1%; P = .017). The response assessment performed on first month after CHRT revealed statistical difference for objective response rate in group 2 when compared with group 1 (P = .04). At the median follow-up of 15.7 months (range, 5-36 months), median overall survival (OS) was 12 months in group 1 (95% CI, 9.1-14.8) and 29.9 months in group 2 (95% CI, 16-43). Median progression-free survival (PFS) was 8 months in group 1 and 15 months in group 2. There was statistically significant difference between the 2 groups regarding OS and PFS (P = .043). CONCLUSION: Our results suggest that OS, PFS, and local control rate are significantly improved with ICT consisting of docetaxel and cisplatin when compared with gemcitabine-cisplatin in inoperable locally advanced NSCLC.

Chronic hereditary pancreatitis with N29I mutation in a Turkish child.

Hereditary pancreatitis, an autosomal dominant disease, is the second most common cause of pancreatitis in children. Here we report a child with recurrent pancreatitis attacks and N29I mutation. Due to the increased risk of pancreatic cancer, taking a detailed past and family history and early diagnosis are important.

Hemophagocytic syndrome associated with visceral leishmaniasis.

Hemophagocytosis, either primary (familial) or secondary (reactive), is a life threatening condition in childhood. Etiology should be vigorously searched to avoid a diagnosis of primary hemophagocytosis and treatment with cytotoxic drugs. A child with visceral leishmaniasis causing hemophagocytosis is presented.

Extrahepatic portal vein thrombosis in children: etiology and long-term follow-up.

OBJECTIVE: Mortality of extrahepatic portal vein thrombosis depends on underlying causes other than gastrointestinal bleeding. The aim of this study was to evaluate the etiology, treatment, and prognosis of patients with extrahepatic portal vein thrombosis. METHODS: The records of 12 patients (age range: 1-9 years) diagnosed with extrahepatic portal vein thrombosis with a minimum follow-up of 2 years were analyzed retrospectively. Their diagnostic evaluations, treatment modalities, complications and long-term follow-ups were noted. RESULTS: Mean follow-up period was 7.4 +/- 3.9 years (2-14 years). Hemorrhage from esophageal varices was the prevalent symptom in 6 patients (50%). Six patients had signs of hypersplenism, 5 were found to have thrombophilia: 2 protein C, 1 protein S, 1 combined protein S, C, and antithrombin III deficiency, and 1 homozygous factor V Leiden mutation. Two patients had congenital cardiovascular abnormalities, and 1 patient developed portal thrombosis after splenectomy operation. None of the patients who started propranolol prophylaxis before first bleeding episode bled during their follow-up periods. Endoscopic sclerotherapy succeed in 66.6% variceal hemorrhages. Shunt surgery was performed in 1 patient. The patients neither faced a life-threatening variceal bleeding nor died during follow-up period. CONCLUSION: Prognosis of extrahepatic portal vein thrombosis is good in childhood. Thrombophilic states are the most frequent precipitating causes. Propranolol for prophylaxis of variceal bleeding and sclerotherapy might be the preferred modalities.