Makbule Eren

Effectiveness and safety of Saccharomyces boulardii for acute infectious diarrhea

Introduction: Acute diarrhea continues to be a leading cause of morbidity, hospitalization and mortality worldwide and probiotics have been proposed as a complementary therapy in the treatment of acute diarrhea. Regarding the treatment of acute diarrhea, a few probiotics including Saccharomyces boulardii seem to be promising therapeutic agents. Areas covered: We performed a systematic review and meta-analysis regarding the use of S. boulardii in the treatment of acute infectious diarrhea with relevant studies that searched with the PubMed, Embase, Scopus, Google Scholar, the Cochrane Controlled Trials Library, and the Cochrane Database of Systematic Reviews through October 2011. This review describes the effects of S. boulardii on the duration of diarrhea, the risk of diarrhea during the treatment (especially at the third day) and duration of hospitalization in patients with acute infectious diarrhea. This review also focused on the potential effects of S. boulardii for acute infectious diarrhea due to different etiological causes. Expert opinion: S. boulardii significantly reduced the duration of diarrhea approximately 24 h and that of hospitalization approximately 20 h. S. boulardii shortened the initial phase of watery stools; mean number of stools started to decrease at day 2; moreover, a significant reduction was reported at days 3 and 4. This systematic review and meta-analysis of the efficacy of S. boulardii in the treatment of acute infectious diarrhea show that there is strong evidence that this probiotic has a clinically significant benefit, whatever the cause, including in developing countries. Therefore, with S. boulardii, the shortened duration of diarrhea and the reduction in hospital stay result in social and economic benefits.

Clinical Efficacy Comparison of Saccharomyces boulardii and Yogurt Fluid in Acute Non-Bloody Diarrhea in Children: A Randomized, Controlled, Open Label Study

The purpose of this trial is to evaluate the clinical efficacy and cost/effectiveness of Saccharomyces boulardii compared with yogurt fluid (YF) in acute non-bloody diarrhea in children. This randomized, prospective open-label clinical trial includes 55 children (36 boys, 19 girls; mean age 21.2 +/- 28.2 months). Group A (N = 28) received lyophilized S. boulardii and group B (N = 27) received YF. The duration of diarrhea was shorter with S. boulardii but the hospital stay was reduced with YF, although these differences were not significant. However, diarrhea had resolved in significantly more children on day 3 in the S. boulardii group (48.5% versus 25.5%; P < 0.05). In outpatient cases, yogurt treatment was cheaper than S. boulardii whereas in hospitalized patients, treatment cost was similar. In conclusion, the effect of daily freshly prepared YF was comparable to S. boulardii in the treatment of acute non-bloody diarrhea in children. The duration of diarrhea was shorter in the S. boulardii group, expressed as a significantly higher number of patients with normal stools on day 3.

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.

Saccharomyces boulardii CNCM I-745 reduces the duration of diarrhoea, length of emergency care and hospital stay in children with acute diarrhoea.

Evidence from the literature has shown that Saccharomyces boulardii provides a clinically significant benefit in the treatment of acute infectious diarrhoea in children. In this multicentre, randomised, prospective, controlled, single blind clinical trial performed in children with acute watery diarrhoea, we aimed to evaluate the impact of S. boulardii CNCM I-745 in hospitalised children, in children requiring emergency care unit (ECU) stay and in outpatient settings. The primary endpoint was the duration of diarrhoea (in hours). Secondary outcome measures were duration of hospitalisation and diarrhoea at the 3(rd) day of intervention. In the whole study group (363 children), the duration of diarrhoea was approximately 24 h shorter in the S. boulardii group (75.4±33.1 vs 99.8±32.5 h, P<0.001). The effect of S. boulardii (diarrhoea-free children) was observed starting at 48 h. After 72 h, only 27.3% of the children receiving probiotic still had watery diarrhoea, in contrast to 48.5% in the control group (P<0.001). The duration of diarrhoea was significantly reduced in the probiotic group in hospital, ECU and outpatient settings (P<0.001, P<0.01 and P<0.001, respectively). The percentage of diarrhoea-free children was significantly larger after 48 and 72 h in all settings. The mean length of hospital stay was shorter with more than 36 h difference in the S. boulardii group (4.60±1.72 vs 6.12±1.71 days, P<0.001). The mean length of ECU stay was shorter with more than 19 h difference in the probiotic group (1.20±0.4 vs 2.0±0.3 days, P<0.001). No adverse effects related to the probiotic were noted. Because treatment can shorten the duration of diarrhoea and reduce the length of ECU and hospital stay, there is likely a social and economic benefit of S. boulardii CNCM I-745 in adjunction to oral rehydration solution in acute infectious gastroenteritis in children.

Safety profile of six months lansoprozole treatment in children

Proton pump inhibitors (PPIs) block acid production through H/K ATPase inhibition which is the final pump in the acid secretion pathway. They are generally well tolerated in the short term both in adults and children. However, prolonged suppression of acid secretion may interfere with absorption of various minerals, vitamins, and hematinic factors [1]. Although parietal cells are the major site for PPI activation, H/K ATPase pumps which are found in leukocytes and osteoclasts may also be a target for PPIs, which may therefore have some other deleterious effects beside gastric acid inhibition. We evaluated the impact of six months’ lansoprazole treatment on hemoglobin (Hb), serum iron (Fe), ferritin, total iron binding capacity (TIBC), vitamin B12, calcium (Ca), phosphate (P), alkaline phosphatase (ALP) level, urine Ca/Cr, bone turnover, bone mineralization, community acquired pneumonia, and acute gastroenteritis in children. Forty-five children (22 female), aged between 4–17 years (mean 12), who were diagnosed as GERD and had received lansoprozole (1–1.4 mg/kg/day, max 60 mg), and sodium alginate (0.25 mg/kg/dose three times a day) for six months during November 2007 to May 2009, were eligible for the study. None of these children had any systemic illness. GERD was diagnosed by 24 hours esophageal pH monitoring. Patients with symptoms suggestive of gastritis or peptic ulcer underwent gastroduodenoscopy. In each visit (2 months interval), parents were asked for signs of acute gastroenteritis and pneumonia in the preceding 2 months and encouraged to get in touch with the clinic in any kind of infectious or adverse event. Endoscopy was performed in 27 patients, and revealed antral gastritis in 19 and mild duodenitis in 14. Among them, 8 patients had also corpus gastritis and 16 had H. pylori infection. H. pylori-infected children were included in the study 8 weeks after H. pylori eradication was achieved. The mean levels of hemoglobin, serum iron, ferritin, total iron binding capacity, Ca, P, alkaline phosphatase, vitamin B12, urine calcium/creatinine ratio, mean L1-4 bone mineral density, and Z score at baseline were similar to those at six months of lansoprazole treatment (Table 1). L1–L4 total bone mineral content increased significantly (55.9%, p=0.021). One patient developed two episodes of pneumonia. None of the patient developed acute gastroenteritis. Gastric acidity reduces ferric iron to the more soluble ferrous form and facilitates iron absorption [2]. Studies indicating the potential of iron deficiency anemia development, with long term PPI treatment in the clinical practice are restricted with only few case reports in adults [3]. We did not detect an association between iron deficiency anemia and lansoprozole treatment in children. Vitamin B12 requires gastric acidity in order to be released from foods [2]. It has been proposed that reduction of M. Eren (*) Department of Pediatrics, Section of Gastroenterology and Hepatology, Eskisehir Osmangazi University, Faculty of Medicine, Eskisehir, Turkey e-mail: makbule99@yahoo.com

Is N-acetylcysteine infusion an effective treatment option in L-asparaginase associated hepatotoxicity?

Fig. 1. Abdominal computed tomography showed a hepatomegaly and hepatosteatosis. REFERENCES 1. Baxter EJ, Scott LM, Campbell PJ, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet 2005;365:1054-61. 2. Scott LM. The JAK2 exon 12 mutations: a comprehensive review. Am J Hematol 2011;86:668-76. 3. Darwish Murad S, Plessier A, Hernandez-Guerra M, et al. Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Intern Med 2009;151:167-75. 4. Milosevic Feenstra JD, Nivarthi H, Gisslinger H, et al. Wholeexome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms. Blood 2016;127: 325-32. 5. Alghasham N, Alnouri Y, Abalkhail H, Khalil S. Detection of mutations in JAK2 exons 12-15 by Sanger sequencing. Int J Lab Hematol 2016;38:34-41.

Time Series Analysis of the Microbiota of Children Suffering From Acute Infectious Diarrhea and Their Recovery After Treatment

Gut microbiota is closely related to acute infectious diarrhea, one of the leading causes of mortality and morbidity in children worldwide. Understanding the dynamics of the recovery from this disease is of clinical interest. This work aims to correlate the dynamics of gut microbiota with the evolution of children who were suffering from acute infectious diarrhea caused by a rotavirus, and their recovery after the administration of a probiotic, Saccharomyces boulardii CNCM I-745. The experiment involved 10 children with acute infectious diarrhea caused by a rotavirus, and six healthy children, all aged between 3 and 4 years. The children who suffered the rotavirus infection received S. boulardii CNCM I-745 twice daily for the first 5 days of the experiment. Fecal samples were collected from each participant at 0, 3, 5, 10, and 30 days after probiotic administration. Microbial composition was characterized by 16S rRNA gene sequencing. Alpha and beta diversity were calculated, along with dynamical analysis based on Taylors law to assess the temporal stability of the microbiota. All children infected with the rotavirus stopped having diarrhea at day 3 after the intervention. We observed low alpha diversities in the first 5 days (p-value < 0.05, Wilcoxon test), larger at 10 and 30 days after probiotic treatment. Canonical correspondence analysis (CCA) showed differences in the gut microbiota of healthy children and of those who suffered from acute diarrhea in the first days (p-value < 0.05, ADONIS test), but not in the last days of the experiment. Temporal variability was larger in children infected with the rotavirus than in healthy ones. In particular, Gammaproteobacteria class was found to be abundant in children with acute diarrhea. We identified the microbiota transition from a diseased state to a healthy one with time, whose characterization may lead to relevant clinical data. This work highlights the importance of using time series for the study of dysbiosis related to diarrhea.