Dermatological Manifestations in Pediatric Inflammatory Bowel Disease.

Background and Objectives: Over the last years, inflammatory bowel disease (IBD) has been reported on a high incidence in pediatric populations and has been associated with numerous extraintestinal manifestations, making its management a real challenge for the pediatric gastroenterologist. Dermatological manifestations in IBD are either specific, related to the disease activity or treatment-associated, or non-specific. This literature review aims to identify and report the dermatological manifestations of IBD in children, the correlation between their appearance and the demographical characteristics, the relationship between these lesions and disease activity, and to highlight the impact of dermatological manifestations on an IBD treatment regime. MATERIALS AND METHODS: A systemic literature review was performed, investigating articles and case reports on dermatological manifestations in children with IBD starting from 2005. A total of 159 potentially suitable articles were identified and after the exclusion process, 75 articles were selected. RESULTS: The most common dermatological manifestations reported in pediatric IBD are erythema nodosum and pyoderma gangrenosum. More rare cases of metastatic Crohn's disease, epidermolysis bullosa acquisita, small-vessel vasculitis, necrotizing vasculitis, leukocytoclastic vasculitis, cutaneous polyarteritis nodosa, and Sweet's syndrome have been reported. Oral manifestations of IBD are divided into specific (tag-like lesions, mucogingivitis, lip swelling with vertical fissures, aphthous stomatitis, and pyostomatitis vegetans) and non-specific. IBD treatment may present with side effects involving the skin and mucosa. Anti-tumor necrosis factor agents have been linked to opportunistic skin infections, psoriasiform lesions, and a potentially increased risk for skin cancer. Cutaneous manifestations such as acrodermatitis enteropathica, purpuric lesions, and angular cheilitis may appear secondary to malnutrition and/or malabsorption. CONCLUSIONS: The correct diagnosis of dermatological manifestations in pediatric IBD is of paramount importance because of their impact on disease activity, treatment options, and a patient's psychological status.

Duodenoscope-Associated Infections beyond the Elevator Channel: Alternative Causes for Difficult Reprocessing.

OBJECTIVES: Duodenoscopes have been widely used for both diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP) procedures, but recently, numerous outbreaks of multidrug-resistant organisms (MDRO) infections have been reported which has led to extensive research for their possible causes. Consequently, the aim of this study is to search for possible duodenoscope surface damages that could provide an alternative and plausible source of infections. MATERIALS AND METHODS: In order to assess both outer and inner surfaces, a duodenoscope was dismantled and samples were taken from the outer resin polymer and from the air/water, elevator, and working (biopsy) channels that were characterized by FTIR, DSC, TGA, AFM, SEM techniques and the antimicrobial activity were tested. RESULTS: Alterations were noticed on both the coating and working channel polymers, with external alterations increasing progressively from the proximal sample to the distal sample near the tip of the scope. However, the results showed that the coating surface was still efficient against bacterial adhesion. Changes in surface texture and also morphological changes were shown. CONCLUSIONS: The study describes the impact of routine procedural use and reprocessing cycles on the duodenoscope, showing that these may possibly make it susceptible to bacterial contamination and MDRO biofilm formation due to difficult reprocessing of the altered surfaces.

Diagnosis of minimal hepatic encephalopathy in a tertiary care center from eastern Romania: validation of the psychometric hepatic encephalopathy score (PHES).

The psychometric hepatic encephalopathy score (PHES) is frequently used as a "gold standard" for the diagnosis of minimal hepatic encephalopathy (MHE). In Romania, there are currently no widely available tests for the detection of MHE. In this study we aimed to standardize the PHES in a healthy Romanian population and to estimate the prevalence of MHE in a group of Romanian patients with liver cirrhosis. A total of 260 healthy volunteers and 106 patients with liver cirrhosis were included in the study. The five neuropsychological tests comprising the PHES were administered to all enroled subjects. Blood samples for routine tests and serum ammonia were collected. In the healthy volunteer group age and education years were found to be predictors of all tests and gender only in two tests: digit symbol test and serial dotting test. The PHES of the healthy volunteer group was 0,43 ± 1,37 and the cut-off between normal and pathological values was set at -3 points. In the liver cirrhosis group the mean PHES was -2,44 ± 3,41, significantly lower than in the control group (p = 0,001). The estimated prevalence of MHE was 34,7 % (37 patients). In patients with cirrhosis there was a significant correlation between PHES and the severity of the liver disease according to Child-Pugh classification (r = 0,529, p = 0,001) and MELD score (r = -0,525, p = 0,001). According to our results, accurate Romanian PHES norms for the diagnosis of MHE have been developed. MHE was diagnosed in a significant proportion of Romanian patients with liver cirrhosis.

Post-Pandemic Burden of COVID-19-Related Restrictions in the Management of Digestive Tract Cancers: A Single Center Study.

The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has required a complete change in the management of patients with gastrointestinal disease who needed to undergo endoscopic procedures. In the second year of the COVID-19 pandemic, due to restrictions for elective endoscopic procedures, a large number of cancer patients were prevented from early diagnosis of several digestive cancers, which has led to a serious burden in the health system that now needs to be dealt with. We designed a prospective study that included patients in whom access to elective endoscopic examinations during the COVID-19 pandemic had been delayed. Our aim was to investigate the impact of the COVID-19 pandemic on the diagnosis rate of digestive tract malignancies in the context of health crisis management that generates an ethical dilemma regarding the balance of utilitarianism versus deontology. Our study shows that the decrease in the number of newly diagnosed gastrointestinal cancers by endoscopy and biopsy during the pandemic restrictions and the delay in diagnosis have had a clear impact on stage migration due to disease progression.

Pediatric Gastroenterology Research.

For several decades, before the 19th century, pediatric pathology was considered to be an annex of adult pathology and treated as a secondary matter in medical practice [...].

Pediatric COVID-19 and Diabetes: An Investigation into the Intersection of Two Pandemics.

Coronavirus disease 2019 (COVID-19) is a complex infectious disease caused by the SARS-CoV-2 virus, and it currently represents a worldwide public health emergency. The pediatric population is less prone to develop severe COVID-19 infection, but children presenting underlying medical conditions, such as diabetes mellitus, are thought to be at increased risk of developing more severe forms of COVID-19. Diabetic children face new challenges when infected with SARS-CoV-2. On one hand, the glycemic values become substantially more difficult to manage as COVID-19 is a predisposing factor for hyperglycemia. On the other hand, alongside other risk factors, high glycemic values are incriminated in modulating immune and inflammatory responses, leading to potentially severe COVID-19 cases in the pediatric population. Also, there are hypotheses of SARS-CoV-2 being diabetogenic itself, but this information is still to be confirmed. Furthermore, it is reported that there was a noticeable increase in the number of cases of new-onset type 2 diabetes among the pediatric population, and the complications in these patients with COVID-19 include the risk of developing autoimmune diseases under the influence of stress. Additionally, children with diabetes mellitus are confronted with lifestyle changes dictated by the pandemic, which can potentially lead to the onset or exacerbation of a potential underlying anxiety disorder or depression. Since the literature contains a series of unknowns related to the impact of COVID-19 in both types of diabetes in children, the purpose of our work is to bring together the data obtained so far and to identify potential knowledge gaps and areas for future investigation regarding COVID-19 and the onset of diabetes type 1 or type 2 among the pediatric population.

Emerging role of the gut microbiome in post-infectious irritable bowel syndrome: A literature review.

Post-infectious irritable bowel syndrome (PI-IBS) is a particular type of IBS, with symptom onset after an acute episode of infectious gastroenteritis. Despite infectious disease resolution and clearance of the inciting pathogen agent, 10% of patients will develop PI-IBS. In susceptible individuals, the exposure to pathogenic organisms leads to a marked shift in the gut microbiota with prolonged changes in host-microbiota interactions. These changes can affect the gut-brain axis and the visceral sensitivity, disrupting the intestinal barrier, altering neuromuscular function, triggering persistent low inflammation, and sustaining the onset of IBS symptoms. There is no specific treatment strategy for PI-IBS. Different drug classes can be used to treat PI-IBS similar to patients with IBS in general, guided by their clinical symptoms. This review summarizes the current evidence for microbial dysbiosis in PI-IBS and analyzes the available data regarding the role of the microbiome in mediating the central and peripheral dysfunctions that lead to IBS symptoms. It also discusses the current state of evidence on therapies targeting the microbiome in the management of PI-IBS. The results of microbial modulation strategies used in relieving IBS symptomatology are encouraging. Several studies on PI-IBS animal models reported promising results. However, published data that describe the efficacy and safety of microbial targeted therapy in PI-IBS patients are scarce. Future research is required.

Severe Acute Pancreatitis Treated with Negative Pressure Wound Therapy System: Influence of Laboratory Markers.

(1) Background: An open abdomen is a serious medical condition that requires prompt and effective treatment to prevent complications and improve patient outcomes. Negative pressure therapy (NPT) has emerged as a viable therapeutic option for temporary closure of the abdomen, offering several benefits over traditional methods. (2) Methods: We included 15 patients with pancreatitis who were hospitalized in the I-II Surgery Clinic of the Emergency County Hospital "St. Spiridon" from Iasi, Romania, between 2011-2018 and received NPT. (3) Results: Preoperatively, the mean IAP level was 28.62 mmHg, decreasing significantly postoperatively to 21.31 mmHg. The mean level of the highest IAP value recorded in pancreatitis patients treated with VAC did not differ significantly by lethality (30.31 vs. 28.50; p = 0.810). In vacuum-treated pancreatitis patients with a IAP level > 12, the probability of survival dropped below 50% during the first 7 days of stay in the ICU, so that after 20 days the probability of survival was approximately 20%. IAP enters the determinism of surgery with a sensitivity of 92.3% and a specificity of 99%, the cut-off value of IAP being 15 mmHg. (4) Conclusions: The timing of surgical decompression in abdominal compartment syndrome is very important. Consequently, it is vital to identify a parameter, easy to measure, within the reach of any clinician, so that the indication for surgical intervention can be made judiciously and without delay.

Is There a Potential Link between Gastroesophageal Reflux Disease and Recurrent Respiratory Tract Infections in Children?

BACKGROUND: The implications of gastroesophageal reflux disease in respiratory tract infections have been investigated over time. The aim of our study was to evaluate the relationship between these two pathologic entities and the outcome after proper antireflux treatment. METHODS: A group of 53 children with recurrent respiratory tract infections admitted in the gastroenterology clinic of a children's hospital in North-East Romania was investigated for gastroesophageal reflux disease through 24 h pH-metry. Those with a Boix-Ochoa score higher than 11.99 received proton pump inhibitor treatment and were reevaluated after 2 months. RESULTS: A total of 41 children were found with a positive Boix-Ochoa score. After 2 months of antireflux therapy, eight patients still had a positive Boix-Ochoa score. CONCLUSIONS: Recurrent respiratory tract infections with symptoms resistant to treatment should be considered a reason to investigate for gastroesophageal reflux, because the symptoms may be due to micro- or macro-aspiration of the gastric refluxate or to an esophageal-bronchial reflex mediated through the vagal nerve.

Evaluation of Disease Activity in Inflammatory Bowel Disease: Diagnostic Tools in the Assessment of Histological Healing.

Inflammatory bowel disease (IBD) comprises two types of chronic intestinal disorders: Crohn's disease and ulcerative colitis. In long-standing ulcerative colitis disease activity, histological persistent inflammation has been linked to an increased risk of relapse, and long-term corticosteroid use, even when endoscopic remission is reached. In Crohn's disease, the discontinuous nature of lesions and transmural inflammation have limited the standardized histological assessment. The current evidence from research proposes that besides clinical and endoscopic healing, the achievement of histological healing constitutes an endpoint to assess disease activity and remission in IBD patients concerning better long-term disease outcomes. Histological alterations may persist even in the absence of endoscopic lesions. For these reasons, new advanced techniques promise to revolutionize the field of IBD by improving the endoscopic and histologic assessment, disease characterization, and ultimately patient care, with an established role in daily practice for objective assessment of lesions. This review outlines the importance of including microscopic evaluation in IBD, highlighting the clinical benefits of a deep state of disease remission using validated diagnostic methods and scoring systems for daily clinical practice.

Pattern of Primary Resistance of Helicobacter pylori to Clarithromycin among Pediatric Patients from North-Eastern Romania.

BACKGROUND: Helicobacter pylori antibiotic resistance has increased worldwide and affects the effectiveness of current therapies. The recommended first-line empiric treatment should be tailored to the local clarithromycin resistance rate. This study aimed to determine the pediatric patient profile and rate of clarithromycin resistance for patients diagnosed with Helicobacter pylori by gastric biopsy. METHODS: We studied 84 positive gastric samples for Helicobacter pylori. Positive results were confirmed by a rapid urease test and histopathological examination, with the type of gastritis established according to the Sydney System. Gastric biopsy samples were stored in RNA saver. Clarithromycin resistance was determined by a real-time polymerase chain reaction-based molecular assay after RNA-DNA extraction. RESULTS: Of the 84 biopsy samples analyzed, 35 (41.6%) were resistant to clarithromycin. Clarithromycin resistance was found mainly in girls (80%) with a mean age of 15 years (range 6-17 years). The history of prior exposure to clarithromycin was 91.6%. The concordance between the histopathological examination and the PCR test was 100%. CONCLUSIONS: One in 2.4 children infected with Helicobacter pylori had a strain resistant to clarithromycin. This resistant strain may be a reason for treatment failure in Romanian children, yet this is uninvestigated. The high rate of bacterial resistance to this antibiotic among children indicates the need for susceptibility testing before therapy.

Magnesium-A Potential Key Player in Inflammatory Bowel Diseases?

The altered magnesium status in inflammatory bowel disease (IBD) patients may have a significant clinical imprint considering its role in cell signaling and genomic stability, as well as its involvement in IBD patients' fatigue. Our study pioneers the investigation of magnesium hair concentration patterns in an adult population of IBD patients. The hair magnesium concentration in IBD patients is compared to healthy controls in order to identify correlations between the magnesium status and relevant parameters related to disease activity, psychological status, and sleep quality. We report a significantly lower hair magnesium concentration within the IBD group compared to healthy controls (95%CI: 0.006-0.062; p = 0.017) and lower levels in CD compared to UC (95%CI: -0.061--0.002; p = 0.038). We identified a borderline statistical significance between the hair magnesium concentration and UC disease activity (95%CI; -0.679-0.008; p = 0.055) and a significantly lower magnesium concentration in patients who reported increased sleep latency (95%CI -0.65--0.102; p = 0.011) or decreased sleep duration (95%CI -0.613--0.041; p = 0.028). Our results advance several hypotheses with substantial clinical impact to be confirmed in future studies. Magnesium levels appear to be modified in IBD patients, which suggests it either plays a primary role in disease pathophysiology or a is result of the disease's evolution. Magnesium could be used in predictive models for clinical/subclinical disease activity. Moreover, magnesium supplementation may improve IBD evolution and sleep quality for patients with a deficit of this mineral. However, confirmatory evidence-based studies are needed to generate specific dosing, time of supplementation, and optimum monitoring of magnesium status in IBD patients.

Helicobacter pylori Infection in a Pediatric Population from Romania: Risk Factors, Clinical and Endoscopic Features and Treatment Compliance.

Background and Objectives: The aim of this study was to investigate the association between H. pylori positivity with specific symptoms, risk factors and endoscopic patterns among the pediatric population in northeastern Romania. Materials and Methods: A prospective study was performed in 18 months on 185 children aged 6−18 years with an indication for upper digestive endoscopy. Demographic, anamnestic, symptomatic, endoscopic and histologic data were recorded. Results: Of 116 H. pylori-positive children, the most affected group was 15−17 years. Most (65.5%) of them were girls, with a significant association (p < 0.001). The majority (66.4%) lived in a rural area and 47.4% of children had an unsafe source of water and lived in overcrowded houses with no basic sanitary comfort. The most frequent symptom was epigastric pain (56.9%), and the main endoscopic appearance was nodularity and hyperemia. Patients diagnosed with H. pylori started triple-therapy treatment for 14 days. Only 13.8% stopped the treatment, mainly because of a misunderstanding of the treatment protocol (9.5%). Conclusions: Romanian teen girls living in rural areas are at high risk for H. pylori infection. Epigastric pain and endoscopic nodularity of the gastric mucosa were associated with the infection. As the resistance of the bacteria is unknown in our country, future research is needed in order to improve the eradication rate.

The Effectiveness of Different Eradication Schemes for Pediatric Helicobacter pylori Infection-A Single-Center Comparative Study from Romania.

INTRODUCTION: In Romania, studies on the pediatric population regarding H. pylori infection or bacterial resistance to antibiotics are limited. Eradication treatment of this infection still raises important problems in medical practice. This study aims to compare the effectiveness of three eradication therapies used against H. pylori infection in the pediatric population. METHODS: The prospective study enrolled children aged 6-17 years who were first diagnosed with H. pylori infection. Patients received a randomized treatment either the therapy with clarithromycin (CLR), the therapy with metronidazole (MTZ) or sequential therapy. The effectiveness of the eradication treatment was evaluated after 4-8 weeks from the end of the therapy by testing fecal antigen. RESULTS: 149 patients were enrolled over 18 months. The eradication rates were 49.5% for the treatment scheme with proton pump inhibitor (PPI) + amoxicillin (AMO) + MTZ, 26.7% for PPI + AMO + CLR and 23.8% for sequential therapy. MTZ therapy was superior to CLR therapy, but sequential therapy was not. Side effects were recorded for PPI + AMO + CLR with 39.6%, followed by sequential therapy 37.7%, and only 22.6% for PPI + AMO + MTZ. CONCLUSIONS: Therapy with MTZ can achieve a higher eradication rate as a first-line treatment in the case of H. pylori infection. Taking into account that Romania is in an area with increased resistance to CLR, MTZ therapy could be a promising alternative.

Risk Predictors of Advanced Fibrosis in Non-Alcoholic Fatty Liver Disease.

The assessment of fibrosis in chronic liver diseases using non-invasive methods is an important topic in hepatology. The aim of this study is to identify patients with non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis by establishing correlations between biological/ultrasound markers and non-invasively measured liver stiffness. This study enrolled 116 patients with non-alcoholic fatty liver disease, which were evaluated clinically, biologically, and by ultrasound. Liver fibrosis was quantified by measuring liver stiffness by shear wave elastography (SWE). Multiple correlation analysis of predictors of liver fibrosis identified a number of clinical, biological, and ultrasound parameters (BMI, blood glucose, albumin, platelet count, portal vein diameter, bipolar spleen diameter) that are associated with advanced liver fibrosis in patients with non-alcoholic fatty liver disease. The correlations between the degree of liver fibrosis and the risk values of some serological and ultrasound markers obtained in our study could be useful in clinical practice for the identification of advanced fibrosis in patients with NAFLD.

Could the burden of pancreatic cancer originate in childhood?

The presence of pancreatic cancer during childhood is extremely rare, and physicians may be tempted to overlook this diagnosis based on age criteria. However, there are primary malignant pancreatic tumors encountered in pediatric patients, such as pancreatoblastoma, and tumors considered benign in general but may present a malignant potential, such as the solid pseudo-papillary tumor, insulinoma, gastrinoma, and vasoactive intestinal peptide secreting tumor. Their early diagnosis and management are of paramount importance since the survival rates tend to differ for various types of these conditions. Many pediatric cancers may present pancreatic metastases, such as renal cell carcinoma, which may evolve with pancreatic metastatic disease even after two or more decades. Several childhood diseases may create a predisposition for the development of pancreatic cancer during adulthood; hence, there is a need for extensive screening strategies and complex programs to facilitate the transition from pediatric to adult healthcare. Nevertheless, genetic studies highlight the fact the specific gene mutations and family aggregations may be correlated with a special predisposition towards pancreatic cancer. This review aims to report the main pancreatic cancers diagnosed during childhood, the most important childhood diseases predisposing to the development of pancreatic malignancies, and the gene mutations associates with pancreatic malignant tumors.

Romanian National Guideline on Translating Fecal Microbiota Transplantation Applications related to Clostridioides difficile Infections into the Local Clinical Practice.

Fecal microbiota transplantation involves the infusion of intestinal microorganisms via the transfer of a stool from a healthy individual into a diseased individual, with the intent of restoring normal intestinal flora. Fecal transplant is proposed for the treatment of refractory Clostridioides difficile infection. At present, recurrent Clostridioides difficile infection is the only indication supported by solid scientific evidence. Regulations by healthcare authorities vary among different countries. Considering that Romania does not have an available national guideline to offer standardization, this paper aimed to create a national fecal microbiota transplantation guideline concerning indications, techniques and donor screening, developed by international and local scientific working groups.

Anatomy of Major Duodenal Papilla Influences ERCP Outcomes and Complication Rates: A Single Center Prospective Study.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) has been one of the most intensely studied endoscopic procedures due to its overall high complication rates when compared to other digestive endoscopy procedures. The safety and outcome of such procedures have been linked to multiple procedure- or patient-related risk factors. The aim of our study is to evaluate whether the morphology of the major duodenal papilla influences the ERCP outcomes and complication rates. METHODS: A total of 322 patients with a native papilla have been included in the study over an eight month period. Morphology of the papilla has been classified into normal papilla and four anatomical variations (Type I-IV). All patients have been prospectively monitored over a 15 day period after ERCP. Procedural outcomes and complication rates have been registered. RESULTS: Morphology of the papilla influences both overall complication rates (95%CI, p = 0.0066) and post-ERCP pancreatitis rates (95%CI, p = 0.01001) in univariate analysis. Type IV papillae have proven to be independent risk factors for post-ERCP pancreatitis in multivariate analysis (OR = 12.176, 95%CI, p = 0.005). Type I papillae have been significantly linked to difficult cannulation (AUC = 0.591, 95%CI, p = 0.008); Conclusions: In the monitored cohort morphology of the major duodenal papilla has significantly influenced both ERCP outcomes and post-procedural complication rates.

Interrelations between elevated alpha-fetoprotein levels and tumor morphology of patients with hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer related deaths worldwide, while at the same time having a constant growth in incidence. A commonly used biomarker in managing liver cancer cases, alpha-fetoprotein (AFP) is losing clinical ground in favor of imaging studies and emerging biomarkers. The study aims to reassess potential prognosis indicators and risk factors for an elevated level of this glycoprotein by analyzing its relationship with macroscopic morphology tumor-related features. PATIENTS, MATERIALS AND METHODS: One hundred and thirty-one newly diagnosed HCC patients had their clinical, tumor and liver disease features investigated in contrast to elevated AFP levels with 200 IU∕mL being used as preferred cut-off. RESULTS: Tumor size =5 cm [odds ratio (OR) 3.36, 95% confidence interval (CI): 1.29-8.74, p=0.013] is an independent tumor-related predictor of markedly elevated AFP values. Noteworthy connections with the type of tumor, multinodular appearance and portal vein thrombosis were also found through univariate analysis. CONCLUSIONS: AFP could still be a reliable tool in diagnosis and prognosis of HCC patients especially in developing countries due to its relevant association with aspects of advanced tumor and liver disease, gender and a poor functional status.

Terahertz Spectroscopy and Imaging: A Cutting-Edge Method for Diagnosing Digestive Cancers.

The Terahertz's wavelength is located between the microwave and the infrared region of the electromagnetic spectrum. Because it is non-ionizing and non-invasive, Terahertz (THz)-based detection represents a very attractive tool for repeated assessments, patient monitoring, and follow-up. Cancer acts as the second leading cause of death in many regions, and current predictions estimate a continuous increasing trend. Of all types of tumors, digestive cancers represent an important percentage and their incidence is expected to increase more rapidly than other tumor types due to unhealthy lifestyle habits. Because it can precisely differentiate between different types of molecules, depending on water content, the information obtained through THz-based scanning could have several uses in the management of cancer patients and, more importantly, in the early detection of different solid tumors. The purpose of this manuscript is to offer a comprehensive overview of current data available on THz-based detection for digestive cancers. It summarizes the characteristics of THz waves and their interaction with tissues and subsequently presents available THz-based technologies (THz spectroscopy, THz-tomography, and THZ-endoscope) and their potential for future clinical use. The third part of the review is focused on highlighting current in vitro and in vivo research progress in the field, for identifying specific digestive cancers known as oral, esophageal, gastric, colonic, hepatic, and pancreatic tumors.