The relationship between small intestinal bacterial overgrowth and constipation in children - a comprehensive review.

Small intestinal bacterial overgrowth (SIBO) is characterized by an increase in the bacterial population of the small intestine due to an imbalance between the amount of bacteria and the intestinal barrier. Pediatric SIBO presents with a wide spectrum of symptoms, ranging from mild gastrointestinal complaints to malabsorption or malnutrition. Breath tests are commonly used as noninvasive diagnostic tools for SIBO, but a standardized methodology is currently unavailable. Intestinal flora produces methane which slows intestinal transit and increases the contractile activity of small intestine. Emerging literature suggests a correlation between overgrowth of methanogenic bacteria in the intestines and constipation. Treatment of SIBO involves administration of antibacterial therapy in addition to management of underlying conditions and optimal dietary adjustments. However, research on antibiotic treatment for pediatric patients with constipation and SIBO is limited and has yielded conflicting results. In the current review, we summarize the state-of-the-art of the field and discuss previous treatment attempts and currently used regimens for SIBO patients with constipation, with a focus on pediatric populations.

Epidemiological and Clinical Aspects in a Cohort of Colorectal Cancer Patients.

We conducted a retrospective, observational study, based on 91 patients diagnosed with colorectal cancer (CRC), hospitalized and evaluated within the Surgical and the 2nd Internal Medicine Clinic, the Clinical Emergency County Hospital Craiova, between October 2020 and October 2022. We aimed in this study to analyze the epidemiological aspects and clinical characteristics of patients with CRC. In our study group, the patients' ages were between 30-89 years, with mean a of 68.06 (±9.39) years. The incidence of CRC cases in young patients was relatively low. 56.04% of all patients lived in urban areas. In 57.14% of cases, tumors were found on the left colon. The histopathological (HP) examination revealed the net predominance of adenocarcinoma. Depending on the HP grade, the tumor formations were represented predominantly by moderate and poorly differentiated tumors, having G2 and G3 grades. The T3 tumors predominated the total tumors identified. We observed that obstructions have the highest percentages on the left colon, while haemorrhages and perforations have higher percentages on the right side of the colon. The results obtained in our study largely validated the hypothesis proposed at the beginning of the study, according to which, using the clinical, paraclinical, and HP data, we can create a typology of the patient with CRC, from the Craiova Reference Center, to guide us in identifying some measures to decrease the percentage of CRC, as well as to improve the efficiency of the surgical treatment for these cases.

Changes in Rat Mammary Tissue Architecture Following Pregnancy/Lactation Exposure to Glyphosate Alone or with 2,4-D and Dicamba.

The current study aimed to assess the possible endocrine disruptor effects on rat mammary tissue and reproductive organs during pregnancy and lactation when exposed to low doses of glyphosate and its combination with 2,4-dichlorophenoxyacetic acid (2,4-D) and dicamba. The study involved the exposure of pregnant Wistar rats to various regulatory-relevant doses of glyphosate, ranging from gestational day 6 until fine of the lactation period. Glyphosate doses corresponded to the European Union's glyphosate-acceptable daily intake (ADI; 0.5mg/kg bw/day) and no observed adverse effect level (NOAEL; 50mg/kg bw/day). The dose of the mixture of glyphosate, dicamba, and 2,4-D was at the European Union ADI for each herbicide namely 0.5, 0.002, and 0.3mg/kg bw/day, respectively. In the animals exposed to glyphosate NOAEL serum estradiol levels were increased compared to untreated animals, along with an upregulation of TNF-?, MMP-2, and MMP-9 as measured in mammary gland homogenates compared to non-treated animals. Moreover, in this group, a focally acute inflammatory infiltrate was observed in the mammary gland. Our study showed that short-term exposure to glyphosate at doses that are set as safe by regulators and thus without risk corroborated with a particular physiological state as gestation and lactation, can give rise to inflammatory changes in breast tissue in rats. These findings support the need for further evaluation of glyphosate and mixtures of glyphosate with other pesticides for public health protection, especially for those categories vulnerable to the potential endocrine disruptor properties of these pesticides such as pregnant women, newborns, and children.

Multidisciplinarity and Trandisciplinarity in the Diagnosis and Treatment of Pediatric Gastrointestinal Diseases.

It is an honor and a privilege to have helped bring this Special Issue titled "Multidisciplinarity and Trandisciplinarity in the Diagnosis and Treatment of Pediatric Gastrointestinal Diseases" to you [...].

The Most Recent Insights into the Roots of Gastric Cancer.

Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to know if the most early premalignant transformation occurs in children or later since, this would enable the development of effective anti-tumorigenesis strategies. The interplay between H. pylori virulence factors, the host's responses modified by this infection, and the gastric microecology are complex and eventually lead to the development of gastric cancer in susceptible individuals. Several biomarkers were identified as major contributors of this long-lasting process, such as pepsinogens, gastrin 17, lipid-, glucose- and iron-metabolism parameters, immunity players, aberrant bacterial DNA methylation, H. pylori virulence factors, and hallmarks of gastric dysbiosis. Several of these biomarkers were also identified in children with H. pylori infection, independently of the presence of premalignant lesions, which were also proven to be present in a subgroup of H. pylori-infected children, especially those carrying extremely virulent strains. Therefore, the most incipient premalignant gastric changes might indeed occur early during childhood, opening a promising research gate for further studies to delineate the border between infection and cancer.

Prebiotics, Probiotics, and Synbiotics-A Research Hotspot for Pediatric Obesity.

Childhood obesity is a major public health problem worldwide with an increasing prevalence, associated not only with metabolic syndrome, insulin resistance, hypertension, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD), but also with psychosocial problems. Gut microbiota is a new factor in childhood obesity, which can modulate the blood lipopolysaccharide levels, the satiety, and fat distribution, and can ensure additional calories to the host. The aim of this review was to assess the differences and the impact of the gut microbial composition on several obesity-related complications such as metabolic syndrome, NAFLD, or insulin resistance. Early dysbiosis was proven to be associated with an increased predisposition to obesity. Depending on the predominant species, the gut microbiota might have either a positive or negative impact on the development of obesity. Prebiotics, probiotics, and synbiotics were suggested to have a positive effect on improving the gut microbiota and reducing cardio-metabolic risk factors. The results of clinical trials regarding probiotic, prebiotic, and synbiotic administration in children with metabolic syndrome, NAFLD, and insulin resistance are controversial. Some of them (Lactobacillus rhamnosus bv-77, Lactobacillus salivarius, and Bifidobacterium animalis) were proven to reduce the body mass index in obese children, and also improve the blood lipid content; others (Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Enterococcus faecium, and fructo-oligosaccharides) failed in proving any effect on lipid parameters and glucose metabolism. Further studies are necessary for understanding the mechanism of the gut microbiota in childhood obesity and for developing low-cost effective strategies for its management.

Associated factors in pediatric patients admitted with severe iron-deficiency anemia in the last seven years - the experience of a single pediatric unit.

OBJECTIVES: To study the causes of iron deficiency, laboratory findings and clinical manifestation of infants aged 6-12 months and children aged 1-3 years diagnosed with severe iron-deficiency anemia. PATIENTS, MATERIALS AND METHODS: We conducted an observational, retrospective single tertiary center study between January 2015 and April 2022, which included 142 children. The control group (patients with no diagnosis of severe iron-deficiency anemia) included 71 patients and the study group (patients diagnosed with severe iron-deficiency anemia) included also 71 patients. Clinical data were retrospectively collected from hospital medical records. Statistical analysis was conducted using Statistical Package for the Social Sciences (SPSS) 25.0 software. RESULTS: Seventy-one children had hemoglobin <7 g∕dL and low values of ferritin/serum iron (22 infants aged 6-12 months and 49 children aged 1-3 years). In both the study and control groups, the male gender was slightly more prevalent. Mother's age at birth and living standard is significantly lower in the study group. We note a higher frequency of premature births (14.08%) in children identified with anemia compared to control group (8.45%). We found a statistically significant distribution of cow's milk consumption among the two groups (p<0.001). Pearson's correlation test revealed a significant positive correlation, indicating that anemia is directly proportional to cow's milk consumption. CONCLUSIONS: The most frequent cause of iron-deficiency anemia in infants and children 1-3 years old was the consumption of cow's milk following incorrect diversification and incomplete prophylaxis of iron-deficiency anemia.

Impact of Helicobacter pylori Infection upon the Evolution and Outcome of Pediatric Immune Thrombocytopenic Purpura: A Comprehensive Review.

In adults with immune thrombocytopenic purpura (ITP), the identification of H. pylori infection and its subsequent eradication proved to aid platelet recovery. Similar findings, at a smaller scale, were allegedly reported by some pediatric studies. This review's objective was to establish the influence of H. pylori infection and its eradication upon platelet count and recovery in pediatric ITP. Three databases, namely Pubmed, Scopus and Web of Science, were searched for pediatric studies which investigated a link between H. pylori infection and thrombocytopenia. The search results retrieved a number of 21 articles which complied to the inclusion and exclusion criteria. Some studies report lower platelet values among children with ITP and documented H. pylori infection, as well as an improve in platelet numbers after H. pylori treatment. However, results are controversial, as multiple authors failed to identify a higher prevalence of H. pylori among children with ITP or a lack of significant change in therapeutic outcome with the addition of an eradication regimen to standard treatment. The main limitations of current pediatric studies remain the small study samples and the short follow-up periods of the included subjects. Hence, the long-term impact of H. pylori in children with ITP is still uncertain.

Vitamin D and Its Association with H. pylori Prevalence and Eradication: A Comprehensive Review.

Taking into account previous data that sustain a relationship between vitamin D deficiency and higher H. pylori infection positivity rates, this review aims to assess the influence of vitamin D deficiency and/or insufficiency upon the prevalence of H. pylori infection and its eradication success. Three major databases were searched for articles that analyzed a relationship between vitamin D status and H. pylori infection. The literature search retrieved a total of 37 reports, after the article selection process. Hypovitaminosis D emerged as a potential risk factor for H. pylori infection, given the higher prevalence of vitamin D deficiency and/or insufficiency among H. pylori-positive subjects. Furthermore, the same type of micronutrient deficiency has been directly linked to H. pylori eradication failure. An inverse linear relationship between vitamin D status and gastric cancer risk exists, but the additional involvement of H. pylori in this correlation is still in question. The potential benefit of oral supplements in enhancing the success of classical therapeutic regimens of H. pylori still requires future research. Future population-based studies from larger geographical areas are warranted to address this subject in more depth.

Effect of perinatal exposure to glyphosate and its mixture with 2,4-D and dicamba on rat dam kidney and thyroid function and offspring's health.

The increasing use of the herbicide mixture of glyphosate, dicamba and 2-4-D to deal with glyphosate-resistant weeds raises concerns regarding human health and environmental risks. This study aimed to evaluate the effects of developmental exposure to glyphosate and a herbicide mixture containing glyphosate, dicamba and 2-4-D on rat dams' kidney and thyroid function and offspring's health. Pregnant Wistar rats were exposed from day-6 of gestation till weaning to regulatory relevant doses of glyphosate corresponding to the European Union (EU) acceptable daily intake (ADI; 0.5 mg/kg bw/day), and the no-observed-adverse-effect level (NOAEL; 50 mg/kg bw/day), and to a mixture of glyphosate, dicamba and 2,4-D all at the EU ADI (0.5, 0.002 and 0.3 mg/kg bw/day) respectively. After weaning the dams were sacrificed and blood and organs were collected. The pups' health was assessed by measuring viability, gestational and anogenital indices. Perinatal exposure to GLY alone and the herbicide mixture resulted in anti-androgenic effects in male offspring. In dams, exposure to glyphosate resulted in kidney glomerular and tubular dysfunction as well as increased thyroid hormone levels in a dose-dependent manner. Furthermore, exposure to the herbicide mixture resulted in effects similar to those observed with glyphosate at the NOAEL, suggesting at least an additive effect of the herbicide mixture at doses individually considered safe for humans.

Challenges in Diagnosis and Therapeutic Approach of Acute on Chronic Liver Failure-A Review of Current Evidence.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute and severe decompensation of chronic liver disease (CLD) correlated with multiple organ failure, poor prognosis, and increased mortality. In 40-50% of ACLF cases, the trigger is not recognized; for many of these patients, bacterial translocation associated with systemic inflammation is thought to be the determining factor; in the other 50% of patients, sepsis, alcohol consumption, and reactivation of chronic viral hepatitis are the most frequently described trigger factors. Other conditions considered precipitating factors are less common, including acute alcoholic hepatitis, major surgery, TIPS insertion, or inadequate paracentesis without albumin substitution. Host response is likely the primary factor predicting ACLF severity and prognosis, the host immune response having a particular significance in this syndrome, together with the inflammatory cascade. The management of ACLF includes both the prevention of the precipitating factors that lead to acute liver decompensation and the support of vital functions, the prevention and management of complications, the estimation of prognosis, and the opportunity for liver transplantation.

Vaccine Hesitancy Phenomenon Evolution during Pregnancy over High-Risk Epidemiological Periods-"Repetitio Est Mater Studiorum".

(1) Background: The recent epidemiological events were high-stress level generators for humanity, particularly for pregnant women, influencing their attitude, behavior, and decisions regarding vaccination during pregnancy or regarding their future child. The aim of this study was to analyze the anti-pertussis vaccination decision-shaping factors in pregnant women during two epidemiological periods: the measles epidemic and the COVID-19 pandemic. (2) Methods: Two groups of pregnant women were invited to be part of a medical education program, having as the main theme the infectious disease risks and their prevention through vaccination. Before launching the program, participants received a 12-item questionnaire. From a total number of 362 pregnant women enrolled in the study, 182 participated in 2019, and 180 participated in 2022. (3) Results: The socio-demographic data revealed that the age of pregnant women participating in medical education programs increased in 2022 by 1.7 years (p < 0.01). In vitro fertilization was reported in a significantly higher proportion (20% in 2022 vs 9.8% in 2019, p < 0.01). Participation in community-initiated educational programs almost doubled during the pandemic time from 18.7% in 2019 to 33.9% in 2022 (p < 0.01). Pertussis vaccine acceptancy (VA) dropped from 85% in 2019 to 44.4% in 2022 (p < 0.01) (4) Conclusions: In this study, we reported fast-growing vaccine hesitancy and severe declared vaccine reluctance. The results of this complex long-term study, which evaluated pregnant women over several years, showed a five-fold increase in the percentage of pregnant women who disagreed with personal pertussis vaccination. This draws attention to the risks of pertussis epidemic outbreaks in pregnant women and their future infants in the first couple of months of life before the initiation of vaccination.

Cyberbullying in teenagers - a true burden in the era of online socialization.

Cyberbullying represents a major concern worldwide, especially among teenagers with major negative psychological impact. We performed a prospective online questionnaire-based study on 316 teenagers in order to assess the prevalence of cyberbullying in Romania, evaluate its psychosocial consequences, and examine the factors that may predispose them to bullying. Almost 50% of the responders stated that they have been previously bullied, with females having a higher risk of being harassed (P = .0043). Most of the victims were bullied on Facebook, Instagram, and video games. More than 53% of the victims included in our study benefit from help. We found that subjects who have been cyberbullied had a significantly higher risk of having bullied friends (P < .0001). Also, we identified a significant association between the teenagers' relationship with the parents and the incidence of bullying (P = .002). Domestic violence and the male gender were significant risk factors for committing cyberbullying (P = .0014/0.0020). Cyberbullying had a negative impact also on the harasser, and previous victims of cyberbullying had a significantly higher risk of becoming bullied (P < .0001). Also, we found a significant association between the type of substance and the perpetration of aggression (P < .0001). Further studies should focus on designing effective strategies in order to decrease the incidence of this harmful online act of bullying.

Molecular prognostic factors in colorectal cancer: 5-year follow-up.

Colorectal cancer (CRC) is a frequently diagnosed and lethal disease. The risk of developing CRC is determined by environmental and genetic factors. Surgical treatment is the main curative modality for patients with CRC up to stage III. In recent years, a special place has been given to biological agents used as targeted therapy following the genetic analysis of the tumor: Bevacizumab (Avastin), Cetuximab (Erbitux), Ziv-aflibercept (Zaltrap). We present a study based on 46 colorectal tumor resection specimens from patients operated for CRC in the Surgery Departments of the Emergency County Clinical Hospital of Craiova, Romania. Histopathological examination and immunohistochemistry staining of tissue sections were performed to determine the degree of aggressiveness. Using the Kaplan-Meier test, we calculated the correlation coefficient between survival time and immunohistochemical prognostic factors. The patients were followed for 60 months postoperatively.

A Sensitive Public Health Issue-The Vaccine Acceptancy and the Anti-Pertussis Immune Status of Pregnant Women from a Romanian Metropolitan Area.

(1) Background: Immunization of pregnant women (PWs) against Bordetella pertussis infection is still a challenging health matter. (2) Methods: We gathered questionnaire data from 180 PWs regarding their expectancies and current opinion on infectious disease prevention. For the group of PWs who agreed to further investigations, the serum levels of Ig G anti-B. pertussis antibodies (IgG-PT) titer were measured and analyzed. (3) Results: A total of 180 PWs completed the questionnaire and 98 (54.44%, study group) accepted to perform the laboratory tests. During the first two pregnancy trimesters, PWs were found to be more willing (compared with the control group) to test for identifying high-risk situations that could affect themselves and their future infant (p < 0.001). Most of the participating PWs (91, 91.9%) had low levels of anti-pertussis antibodies (values < 40 IU/mL). Declared vaccine coverage of the PWs newborn infants for DTaP-1 and Prevenar 13 (at 2 months) and DTaP-2 and Prevenar 13 (at 4 months) vaccination reached 100% in the study group, while in the control group only 30/82 (36.59%) PWs accepted to be vaccinated during pregnancy, none of them providing data on their infants' vaccine coverage. (4) Conclusions: Enrolled PWs faced a waning immunity against the B. pertussis infection. By raising maternal confidence in the protective role of vaccines against infectious diseases, better vaccine acceptance and better infant vaccine coverage can be achieved.

Not Every Dyspepsia Is Related to Helicobacter pylori-A Case of Esophageal Inlet Patch in a Female Teenager.

Helicobacter pylori infection is one of the main causes of dyspepsia, but it is not the only cause. Esophageal inlet patches are areas of heterotopic gastric mucosa within the esophagus and are commonly located in the cervical part of the esophagus. We report the case of a 16-year-old female, previously known to display symptoms of anxiety, who was admitted to our clinic for dyspeptic symptoms lasting for approximately 1 month in spite of the treatment with proton pump inhibitors. The clinical exam revealed only abdominal tenderness in the epigastric area, while routine laboratory tests showed no abnormalities. The upper digestive endoscopy revealed a well-circumscribed salmon-pink-colored oval lesion of approximately 10 mm in the cervical esophagus, along with hyperemia of the gastric mucosa and biliary reflux. The histopathological exam established the diagnosis of esophageal inlet patch with heterotopic antral-type gastric mucosa and also revealed regenerative changes within the gastric mucosa. We continued to treat the patient with proton pump inhibitors, as well as ursodeoxycholic acid, with favorable evolution. Although rare or underdiagnosed, esophageal inlet patches should never be underestimated and all gastroenterologists should be aware of their presence when performing an upper digestive examination in a patient with dyspeptic symptoms.

Current Worldwide Trends in Pediatric Helicobacter pylori Antimicrobial Resistance.

Helicobacter pylori (H. pylori) has acquired several resistance mechanisms in order to escape the currently used eradication regimens such as mutations that impair the replication, recombination, and transcription of DNA; the antibiotics capability to interact with protein synthesis and ribosomal activity; the adequate redox state of bacterial cells; or the penicillin-binding proteins. The aim of this review was to identify the differences in pediatric H. pylori antimicrobial-resistance trends between continents and countries of the same continent. In Asian pediatric patients, the greatest antimicrobial resistance was found to metronidazole (>50%), probably due to its wide use for parasitic infections. Aside from the increased resistance to metronidazole, the reports from different Asian countries indicated also high resistance rates to clarithromycin, suggesting that ciprofloxacin-based eradication therapy and bismuth-based quadruple therapy might be optimal choices for the eradication of H. pylori in Asian pediatric population. The scarce evidence for America revealed that H. pylori strains display an increased resistance to clarithromycin (up to 79.6%), but not all studies agreed on this statement. Pediatric patients from Africa also presented the greatest resistance rate to metronidazole (91%), but the results in terms of amoxicillin remain contradictory. Nevertheless, the lowest resistance rates in most of the African studies were found for quinolones. Among European children, the most frequent antimicrobial resistance was also noticed for metronidazole and clarithromycin (up to 59% and 45%) but with a predominance for clarithromycin as compared to other continents. The differences in antibiotic use among continents and countries worldwide is clearly responsible for the discrepancies regarding H. pylori antimicrobial-resistance patterns, emphasizing the crucial role of global judicious antibiotic use in order to control the increasing resistance rates worldwide.

Pathogen-Specific Benefits of Probiotic and Synbiotic Use in Childhood Acute Gastroenteritis: An Updated Review of the Literature.

Probiotics represent viable microorganisms which are found within the normal gut microbiota, that exert strain-specific benefits in the management of several gastrointestinal disorders in children, including acute gastroenteritis. This review aims to evaluate the pathogen-specific role of probiotic supplementation in childhood diarrhea. A search of scientific databases was conducted to identify studies which investigated efficacy of probiotics and synbiotics in influencing outcome of acute gastroenteritis of known etiology. We identified 32 studies, most of which analyzed impact of probiotic supplementation in rotavirus gastroenteritis, while a very limited number of these conducted a separate analysis on bacterial diarrhea. Lactobacillus rhamnosus (L. rhamnosus), L. reuteri and S. boulardii still remain the most researched strains, with a proven role in decreasing diarrhea and hospitalization duration, especially in the setting of rotavirus infection. Combined products containing at least one of the aforementioned strains also performed similarly and might also influence rotavirus fecal shedding. Rotavirus immunization status has also been proposed as a significant influencing factor of probiotic use impact. The paucity of research focusing on bacterial etiologies, as well as of clinical trials conducted within ambulatory care units leaves room for further research on the matter, which needs to include larger cohort studies.

Role of Iron Deficiency in Heart Failure-Clinical and Treatment Approach: An Overview.

BACKGROUND: The association of chronic heart failure (CHF) and iron deficiency (ID) with or without anemia is frequently encountered in current medical practice and has a negative prognostic impact, worsening patients' exercise capacity and increasing hospitalization costs. Moreover, anemia is common in patients with chronic kidney disease (CKD) and CHF, an association known as cardio-renal anemia syndrome (CRAS) possessing a significantly increased risk of death. AIM: This review aims to provide an illustrative survey on the impact of ID in CHF patients-based on physiopathological traits, clinical features, and the correlation between functional and absolute ID with CHF-and the benefit of iron supplementation in CHF. METHOD: We selected the most recent publications with important scientific content covering the association of CHF and ID with or without anemia. DISCUSSIONS: An intricate physiopathological interplay is described in these patients-decrease in erythropoietin levels, activation of the renin-angiotensin-aldosterone system, systemic inflammation, and increases in hepcidin levels. These mechanisms amplify anemia, CHF, and CKD severity and worsen patients' outcomes. CONCLUSIONS: Anemia is frequently encountered in CHF and represents a negative prognostic factor. Data from randomized controlled trials have underlined the administration of intravenous iron therapy (ferric carboxymaltose) as the only viable treatment option, with beneficial effects on quality of life and exercise capacity in patients with ID and systolic heart failure.

Immunoexpression of Mismatch Repair Proteins in a Cohort of Colorectal Cancer Patients.

One of the molecular routes of colorectal carcinogenesis is the lack of mismatch repair (MMR) proteins, which may have substantial clinical consequences in predicting therapy success. This study aimed to analyze the expression of the MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), and MutS homolog 6 (MSH6) in a cohort of 91 colorectal cancer (CRC) patients, and to evaluate the relationship between patient clinicopathological characteristics and immunoexpression of these biomarkers. In this study, we obtained the highest scores of the MLH1 immunoexpression in non-mucinous tumors, moderately differentiated lesions, and in stage IV. The highest values of the MSH2 and MSH6 scores were observed in mucinous tumors, and poorly differentiated lesions, in stages II-III, and stages III-IV, respectively. To improve the stratification criteria for targeted oncological therapy and to predict patient outcomes, markers used may help evaluate the aggressiveness of lesions.